BUB3: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
m (Bot: HTTP→HTTPS)
imported>Boghog
(consistent citation formatting; removed further reading citations not specific to this gene)
 
Line 1: Line 1:
{{Infobox_gene}}
{{Infobox_gene}}
'''Mitotic checkpoint protein BUB3''' is a [[protein]] that in humans is encoded by the ''BUB3'' [[gene]].<ref name="pmid9660858">{{cite journal | vauthors = Taylor SS, Ha E, McKeon F | title = The human homologue of Bub3 is required for kinetochore localization of Bub1 and a Mad3/Bub1-related protein kinase | journal = J Cell Biol | volume = 142 | issue = 1 | pages = 1–11 |date=Aug 1998 | pmid = 9660858 | pmc = 2133037 | doi =10.1083/jcb.142.1.1 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: BUB3 BUB3 budding uninhibited by benzimidazoles 3 homolog (yeast)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9184| accessdate = }}</ref>
'''Mitotic checkpoint protein BUB3''' is a [[protein]] that in humans is encoded by the ''BUB3'' [[gene]].<ref name="pmid9660858">{{cite journal | vauthors = Taylor SS, Ha E, McKeon F | title = The human homologue of Bub3 is required for kinetochore localization of Bub1 and a Mad3/Bub1-related protein kinase | journal = The Journal of Cell Biology | volume = 142 | issue = 1 | pages = 1–11 | date = July 1998 | pmid = 9660858 | pmc = 2133037 | doi = 10.1083/jcb.142.1.1 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: BUB3 BUB3 budding uninhibited by benzimidazoles 3 homolog (yeast)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9184| access-date = }}</ref>


Bub3 is a protein involved with the regulation of the [[Spindle checkpoint|Spindle Assembly Checkpoint (SAC)]]; though BUB3 is non-essential in yeast, it is essential in higher eukaryotes. As one of the checkpoint proteins, Bub3 delays the irreversible onset of [[anaphase]] through direction of [[kinetochore]] localization during [[prometaphase]]<ref name="pmid9660858"/> to achieve biorentation. In directing the kinetochore-microtubule interaction, this ensures the proper (and consequenctly, bioriented) attachment of the chromosomes prior to anaphase. Bub3 and its related proteins that form the Spindle Assembly Checkpoint (SAC) inhibit the action of the [[Anaphase-promoting complex|Anaphase Promoting Complex (APC)]], preventing early anaphase entry and mitotic exit; this serves as a mechanism for the fidelity of chromosomal segregation.<ref name="morgan">{{cite book | author = Morgan, David O | title = The cell cycle: principles of control | publisher = Published by New Science Press in association with Oxford University Press | location = London | year = 2007 | isbn = 0-87893-508-8 }}</ref>
Bub3 is a protein involved with the regulation of the [[Spindle checkpoint|Spindle Assembly Checkpoint (SAC)]]; though BUB3 is non-essential in yeast, it is essential in higher eukaryotes. As one of the checkpoint proteins, Bub3 delays the irreversible onset of [[anaphase]] through direction of [[kinetochore]] localization during [[prometaphase]]<ref name="pmid9660858"/> to achieve biorentation. In directing the kinetochore-microtubule interaction, this ensures the proper (and consequenctly, bioriented) attachment of the chromosomes prior to anaphase. Bub3 and its related proteins that form the Spindle Assembly Checkpoint (SAC) inhibit the action of the [[Anaphase-promoting complex|Anaphase Promoting Complex (APC)]], preventing early anaphase entry and mitotic exit; this serves as a mechanism for the fidelity of chromosomal segregation.<ref name="morgan">{{cite book | author = Morgan, David O | title = The cell cycle: principles of control | publisher = Published by New Science Press in association with Oxford University Press | location = London | year = 2007 | isbn = 978-0-87893-508-6 }}</ref>


== Function ==
== Function ==


Bub3 is a crucial component in the formation of the mitotic spindle assembly complex, which forms a complex with other important proteins.<ref name="Kalitsis_2000">{{cite journal | vauthors = Kalitsis P, Earle E, Fowler KJ, Choo KH | title = Bub3 gene disruption in mice reveals essential mitotic spindle checkpoint function during early embryogenesis | journal = Genes Dev. | volume = 14 | issue = 18 | pages = 2277–82 |date=September 2000 | pmid = 10995385 | pmc = 316933 | doi = 10.1101/gad.827500 }}</ref>  For correct segregation of the cells it is necessary for all mitotic spindles to attach correctly to the kinetochore of each chromosome. This is controlled by the mitotic spindle checkpoint complex which operates as a feedback-response.<ref name="Kalitsis_2000"/>  If there is a signal of a defect in the attachment, mitosis will be stopped to ensure that all chromosomes have an amphitelic binding to spindles. After the error is corrected, the cell will proceed to anaphase. The complex of proteins which regulate the cell arrest are [[BUB1]], [[TBC1D1|BUB2]], BUB3 (this protein), [[Mad1]], [[MAD2L1|Mad2]], [[MXD3|Mad3]] and [[KLK4|MPS1]].<ref name="Kalitsis_2000"/>
Bub3 is a crucial component in the formation of the mitotic spindle assembly complex, which forms a complex with other important proteins.<ref name="Kalitsis_2000">{{cite journal | vauthors = Kalitsis P, Earle E, Fowler KJ, Choo KH | title = Bub3 gene disruption in mice reveals essential mitotic spindle checkpoint function during early embryogenesis | journal = Genes & Development | volume = 14 | issue = 18 | pages = 2277–82 | date = September 2000 | pmid = 10995385 | pmc = 316933 | doi = 10.1101/gad.827500 }}</ref>  For correct segregation of the cells it is necessary for all mitotic spindles to attach correctly to the kinetochore of each chromosome. This is controlled by the mitotic spindle checkpoint complex which operates as a feedback-response.<ref name="Kalitsis_2000"/>  If there is a signal of a defect in the attachment, mitosis will be stopped to ensure that all chromosomes have an amphitelic binding to spindles. After the error is corrected, the cell will proceed to anaphase. The complex of proteins which regulate the cell arrest are [[BUB1]], [[TBC1D1|BUB2]], BUB3 (this protein), [[Mad1]], [[MAD2L1|Mad2]], [[MXD3|Mad3]] and [[KLK4|MPS1]].<ref name="Kalitsis_2000"/>


== Role in the spindle assembly checkpoint ==
== Role in the spindle assembly checkpoint ==


At unattached kinetochores, a complex consisting of [[BUB1B|BubR1]], Bub3, and [[Cdc20]] interact with the Mad2-Cdc20 complex to inhibit the APC, thus inhibiting the formation of active APC<sup>Cdc20</sup>.<ref>*{{cite journal | author= Eytan, E.  | author2= Braunstein, I.  | author3= Ganoth, D. |title= Two different mitotic checkpoint inhibitors of the anaphase-promoting complex/cyclosome antagonize the action of the activator Cdc20 |journal= Proc Natl Acad Sci USA |volume=105 |issue= 7 |pages= 9181–9185|year= 2008 |pmid= 18591651|doi= 10.1073/pnas.0804069105 | pmc= 2453698|display-authors=etal}}</ref><ref>*{{cite journal | vauthors= Fang G, Yu H, Kirschner MW| last-author-amp= yes|title= Direct binding of CDC20 protein family members activates the anaphase-promoting complex in mitosis and G1 |journal= Mol Cell |volume=2 |pages= 163–171 |year= 1998 |pmid= 9734353 | doi= 10.1016/S1097-2765(00)80126-4 | issue= 2}}</ref> Bub3 binds constitutively to BubR1; in this arrangement, Bub3 acts as a key component of the SAC in the formation of an inhibitory complex.<ref name="Fraschini"/> [[Securin]] and [[cyclin B]] are also stabilized before the anaphase transition by the unattached kinetochores.<ref>*{{cite journal | author= Li, M.  | author2= Li, S.  | author3= Yuan, J.  | author4= Wang, Z-B  | author5= Sun, S-C  |title= Bub3 Is a Spindle Assembly Checkpoint Protein Regulating Chromosome Segregation during Mouse Oocyte Meiosis |journal= PLoS ONE |volume=4 |issue=11 |pages= e7701|year= 2009 |pmid= 19888327|doi= 10.1371/journal.pone.0007701 | pmc= 2765619  | editor1-last= Jin | editor1-first= Dong-Yan|display-authors=etal}}</ref> The stabilization of cyclin and securin prevent the degradation that would lead to the irreversible and fast separation of the [[sister chromatids]].
At unattached kinetochores, a complex consisting of [[BUB1B|BubR1]], Bub3, and [[Cdc20]] interact with the Mad2-Cdc20 complex to inhibit the APC, thus inhibiting the formation of active APC<sup>Cdc20</sup>.<ref>* {{cite journal | vauthors = Eytan E, Braunstein I, Ganoth D, Teichner A, Hittle JC, Yen TJ, Hershko A | title = Two different mitotic checkpoint inhibitors of the anaphase-promoting complex/cyclosome antagonize the action of the activator Cdc20 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 27 | pages = 9181–5 | date = July 2008 | pmid = 18591651 | pmc = 2453698 | doi = 10.1073/pnas.0804069105 | bibcode = 2008PNAS..105.9181E }}</ref><ref>* {{cite journal | vauthors = Fang G, Yu H, Kirschner MW | title = Direct binding of CDC20 protein family members activates the anaphase-promoting complex in mitosis and G1 | journal = Molecular Cell | volume = 2 | issue = 2 | pages = 163–71 | date = August 1998 | pmid = 9734353 | doi = 10.1016/S1097-2765(00)80126-4 | last-author-amp = yes }}</ref> Bub3 binds constitutively to BubR1; in this arrangement, Bub3 acts as a key component of the SAC in the formation of an inhibitory complex.<ref name="Fraschini"/> [[Securin]] and [[cyclin B]] are also stabilized before the anaphase transition by the unattached kinetochores.<ref>* {{cite journal | vauthors = Li M, Li S, Yuan J, Wang ZB, Sun SC, Schatten H, Sun QY | title = Bub3 is a spindle assembly checkpoint protein regulating chromosome segregation during mouse oocyte meiosis | journal = PloS One | volume = 4 | issue = 11 | pages = e7701 | date = November 2009 | pmid = 19888327 | pmc = 2765619 | doi = 10.1371/journal.pone.0007701 | editor1-last = Jin | bibcode = 2009PLoSO...4.7701L | editor1-first = Dong-Yan }}</ref> The stabilization of cyclin and securin prevent the degradation that would lead to the irreversible and fast separation of the [[sister chromatids]].


The formation of these “inhibitory complexes” and steps feed into a ‘wait’ signal before activation of [[separase]]; at the stage prior to anaphase, securin inhibits the activity of separase and maintains the [[Cohesion (chemistry)|cohesion]] complex.<ref name="morgan"/>
The formation of these “inhibitory complexes” and steps feed into a ‘wait’ signal before activation of [[separase]]; at the stage prior to anaphase, securin inhibits the activity of separase and maintains the [[Cohesion (chemistry)|cohesion]] complex.<ref name="morgan"/>


==Structure==
== Structure ==


The crystal structure of Bub3 indicates a protein of the seven-bladed beta-propeller structure with the presence of [[WD40 repeat]]s, with each blade formed by four anti-parallel [[beta sheet]] strands that have been organized around a tapered channel. Mutation data suggest several important surfaces of interaction for the formation of the SAC, particularly the conserved tryptophans (in blades 1 and 3) and the conserved VAVE sequences in blade 5.
The crystal structure of Bub3 indicates a protein of the seven-bladed beta-propeller structure with the presence of [[WD40 repeat]]s, with each blade formed by four anti-parallel [[beta sheet]] strands that have been organized around a tapered channel. Mutation data suggest several important surfaces of interaction for the formation of the SAC, particularly the conserved tryptophans (in blades 1 and 3) and the conserved VAVE sequences in blade 5.


[[RAE1|Rae1]] (an mRNA export factor), another member of the [[WD40 repeat|WD40]] protein family, shows high sequence conservation with that of Bub3. Both bind to Gle2p-binding-sequence (GLEBS) motifs; while Bub3 specifically binds Mad3 and [[BUB1|Bub1]], Rae1 has more promiscuous binding as it binds both the nuclear pore complex and Bub1. This indicates a similarity in interaction of Bub3 and Rae1 with Bub1.<ref name="crystal">*{{cite journal | author= Larsen, N.A.  | author2= Harrison, S.C.  |title= Crystal structure of the spindle assembly checkpoint protein Bub3 |journal= J Mol Biol |volume=344 |issue=4 |pages= 885–92 |year= 2004 |pmid= 15544799 |doi=10.1016/j.jmb.2004.09.094 }}</ref>
[[RAE1|Rae1]] (an mRNA export factor), another member of the [[WD40 repeat|WD40]] protein family, shows high sequence conservation with that of Bub3. Both bind to Gle2p-binding-sequence (GLEBS) motifs; while Bub3 specifically binds Mad3 and [[BUB1|Bub1]], Rae1 has more promiscuous binding as it binds both the nuclear pore complex and Bub1. This indicates a similarity in interaction of Bub3 and Rae1 with Bub1.<ref name="crystal">* {{cite journal | vauthors = Larsen NA, Harrison SC | title = Crystal structure of the spindle assembly checkpoint protein Bub3 | journal = Journal of Molecular Biology | volume = 344 | issue = 4 | pages = 885–92 | date = December 2004 | pmid = 15544799 | doi = 10.1016/j.jmb.2004.09.094 }}</ref>


==Interactions==
== Interactions ==


BUB3 has been shown to interact with [[BUB1B]],<ref name="pmid9660858"/><ref>*{{cite journal | author= Sudakin, V  | author2= Chan G K, Yen T J |title= Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2 |journal= J. Cell Biol. |volume=154 |issue=5 |pages= 925–36 |year= 2001 |pmid= 11535616 |doi= 10.1083/jcb.200102093 |pmc=2196190}}</ref><ref>*{{cite journal | author= Cayrol, C.  | author2= Cougoule, C.  | author3= Wright, M. |title= The beta2-adaptin clathrin adaptor interacts with the mitotic checkpoint kinase BubR1 |journal= Biochem. Biophys. Res. Commun. |volume=298 |issue=5 |pages= 720–30 |year= 2002 |pmid= 12419313|doi=10.1016/S0006-291X(02)02522-6 }}</ref> [[HDAC1]]<ref name="Yoonetal">*{{cite journal | author= Yoon, Y-M  | author2= Baek, K-H  | author3= Jeong, S-J |title= WD repeat-containing mitotic checkpoint proteins act as transcriptional repressors during interphase |journal= FEBS Lett.  |volume=575 |issue=1–3|pages= 23–9 |year= 2004 |pmid= 15388328 |doi= 10.1016/j.febslet.2004.07.089|display-authors=etal}}</ref> and [[Histone deacetylase 2]].<ref name="Yoonetal"/>
BUB3 has been shown to interact with [[BUB1B]],<ref name="pmid9660858"/><ref>* {{cite journal | vauthors = Sudakin V, Chan GK, Yen TJ | title = Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2 | journal = The Journal of Cell Biology | volume = 154 | issue = 5 | pages = 925–36 | date = September 2001 | pmid = 11535616 | pmc = 2196190 | doi = 10.1083/jcb.200102093 }}</ref><ref>* {{cite journal | vauthors = Cayrol C, Cougoule C, Wright M | title = The beta2-adaptin clathrin adaptor interacts with the mitotic checkpoint kinase BubR1 | journal = Biochemical and Biophysical Research Communications | volume = 298 | issue = 5 | pages = 720–30 | date = November 2002 | pmid = 12419313 | doi = 10.1016/S0006-291X(02)02522-6 }}</ref> [[HDAC1]]<ref name="Yoonetal">* {{cite journal | vauthors = Yoon YM, Baek KH, Jeong SJ, Shin HJ, Ha GH, Jeon AH, Hwang SG, Chun JS, Lee CW | title = WD repeat-containing mitotic checkpoint proteins act as transcriptional repressors during interphase | journal = FEBS Letters | volume = 575 | issue = 1-3 | pages = 23–9 | date = September 2004 | pmid = 15388328 | doi = 10.1016/j.febslet.2004.07.089 }}</ref> and [[Histone deacetylase 2]].<ref name="Yoonetal"/>


Bub3 has been shown to form complexes with [[Mad1]]-Bub1 and with [[Cdc20]] (the interaction of which does not require intact kinetochores). Additionally, it has been shown to bind [[MAD2|Mad2]] and Mad3.<ref name="Fraschini">*{{cite journal | author= Fraschini, R.  | author2= Beretta, A.  | author3= Sironi, L.  | author4= Musacchio, A.  |title= Bub3 interaction with Mad2, Mad3 and Cdc20 is mediated by WD40 repeats and does not require intact kinetochores |journal= The EMBO Journal |volume=20 |issue= 23|pages= 6648–6659 |year= 2001 |pmid= 11726501|doi= 10.1093/emboj/20.23.6648 | pmc= 125326|display-authors=etal}}</ref><ref>*{{cite journal | author= Logarinho, E.  | author2= Bousbaa, H. |title= Kinetochore-microtubule interactions "in check" by Bub1, Bub3 and BubR1: The dual task of attaching and signalling |journal= Cell Cycle |volume=7 |issue= 12 |pages= 1763–1768|year= 2008 |pmid= 18594200 |doi= 10.4161/cc.7.12.6180}}</ref>
Bub3 has been shown to form complexes with [[Mad1]]-Bub1 and with [[Cdc20]] (the interaction of which does not require intact kinetochores). Additionally, it has been shown to bind [[MAD2|Mad2]] and Mad3.<ref name="Fraschini">* {{cite journal | vauthors = Fraschini R, Beretta A, Sironi L, Musacchio A, Lucchini G, Piatti S | title = Bub3 interaction with Mad2, Mad3 and Cdc20 is mediated by WD40 repeats and does not require intact kinetochores | journal = The EMBO Journal | volume = 20 | issue = 23 | pages = 6648–59 | date = December 2001 | pmid = 11726501 | pmc = 125326 | doi = 10.1093/emboj/20.23.6648 }}</ref><ref>* {{cite journal | vauthors = Logarinho E, Bousbaa H | title = Kinetochore-microtubule interactions "in check" by Bub1, Bub3 and BubR1: The dual task of attaching and signalling | journal = Cell Cycle | volume = 7 | issue = 12 | pages = 1763–8 | date = June 2008 | pmid = 18594200 | doi = 10.4161/cc.7.12.6180 }}</ref>
   
   
Bub3 directs the localization of Bub1 at the kinetochore in order to activate the SAC.<ref name="pmid9660858"/> In both ''[[Saccharomyces cerevisiae]]'' and metazoans, Bub3 has been show to bind BubR1 and Bub1.<ref name="morgan"/>
Bub3 directs the localization of Bub1 at the kinetochore in order to activate the SAC.<ref name="pmid9660858"/> In both ''[[Saccharomyces cerevisiae]]'' and metazoans, Bub3 has been show to bind BubR1 and Bub1.<ref name="morgan"/>
Line 32: Line 32:
==Regulation==
==Regulation==


When the SAC is activated, the production of the Bub3-Cdc20 complex is activated. After kinetochore attachment is complete, the spindle checkpoint complexes (including the BubR1-Bub3) experience a decrease in concentration.<ref>*{{cite journal | author= Yu, H.  |title= Regulation of APC–Cdc20 by the spindle checkpoint |journal= Current Opinion in Cell Biology |volume=14 |issue=6 |pages= 706–714 |year= 2002 |pmid= 12473343|doi= 10.1016/S0955-0674(02)00382-4}}</ref><ref name="Doncic">*{{cite journal | author= Doncic, A.  | author2= Ben-Jacob, E.  | author3= Einav, S.  | author4= Barkai, N.  |title= Reverse Engineering of the Spindle Assembly Checkpoint |journal= PLoS ONE |volume=4 |issue=8 |pages= e6495|year= 2009 |pmid= 19652707|doi= 10.1371/journal.pone.0006495 | pmc= 2714964  | editor1-last= Khanin | editor1-first= Raya}}</ref>
When the SAC is activated, the production of the Bub3-Cdc20 complex is activated. After kinetochore attachment is complete, the spindle checkpoint complexes (including the BubR1-Bub3) experience a decrease in concentration.<ref>* {{cite journal | vauthors = Yu H | title = Regulation of APC-Cdc20 by the spindle checkpoint | journal = Current Opinion in Cell Biology | volume = 14 | issue = 6 | pages = 706–14 | date = December 2002 | pmid = 12473343 | doi = 10.1016/S0955-0674(02)00382-4 }}</ref><ref name="Doncic">* {{cite journal | vauthors = Doncic A, Ben-Jacob E, Einav S, Barkai N | title = Reverse engineering of the spindle assembly checkpoint | journal = PloS One | volume = 4 | issue = 8 | pages = e6495 | date = August 2009 | pmid = 19652707 | pmc = 2714964 | doi = 10.1371/journal.pone.0006495 | editor1-last = Khanin | bibcode = 2009PLoSO...4.6495D | editor1-first = Raya }}</ref>


Bub3 also acts as a regulator in that it affects binding of Mad3 to Mad2.<ref name="Fraschini"/>
Bub3 also acts as a regulator in that it affects binding of Mad3 to Mad2.<ref name="Fraschini"/>
Line 60: Line 60:
* Coli polyposis
* Coli polyposis


==References==
== References ==
{{reflist|35em}}
{{reflist|32em}}


==External links==
== Further reading ==
{{refbegin|32em}}
* {{cite journal | vauthors = Cahill DP, da Costa LT, Carson-Walter EB, Kinzler KW, Vogelstein B, Lengauer C | title = Characterization of MAD2B and other mitotic spindle checkpoint genes | journal = Genomics | volume = 58 | issue = 2 | pages = 181–7 | date = June 1999 | pmid = 10366450 | doi = 10.1006/geno.1999.5831 }}
* {{cite journal | vauthors = Kwon TK, Hawkins AL, Griffin CA, Gabrielson E | title = Assignment of BUB3 to human chromosome band 10q26 by in situ hybridization | journal = Cytogenetics and Cell Genetics | volume = 88 | issue = 3-4 | pages = 202–3 | year = 2000 | pmid = 10828586 | doi = 10.1159/000015547 }}
* {{cite journal | vauthors = Saffery R, Irvine DV, Griffiths B, Kalitsis P, Choo KH | title = Components of the human spindle checkpoint control mechanism localize specifically to the active centromere on dicentric chromosomes | journal = Human Genetics | volume = 107 | issue = 4 | pages = 376–84 | date = October 2000 | pmid = 11129339 | doi = 10.1007/s004390000386 }}
* {{cite journal | vauthors = Kaplan KB, Burds AA, Swedlow JR, Bekir SS, Sorger PK, Näthke IS | title = A role for the Adenomatous Polyposis Coli protein in chromosome segregation | journal = Nature Cell Biology | volume = 3 | issue = 4 | pages = 429–32 | date = April 2001 | pmid = 11283619 | doi = 10.1038/35070123 }}
* {{cite journal | vauthors = Sudakin V, Chan GK, Yen TJ | title = Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2 | journal = The Journal of Cell Biology | volume = 154 | issue = 5 | pages = 925–36 | date = September 2001 | pmid = 11535616 | pmc = 2196190 | doi = 10.1083/jcb.200102093 }}
* {{cite journal | vauthors = Saxena A, Saffery R, Wong LH, Kalitsis P, Choo KH | title = Centromere proteins Cenpa, Cenpb, and Bub3 interact with poly(ADP-ribose) polymerase-1 protein and are poly(ADP-ribosyl)ated | journal = The Journal of Biological Chemistry | volume = 277 | issue = 30 | pages = 26921–6 | date = July 2002 | pmid = 12011073 | doi = 10.1074/jbc.M200620200 }}
* {{cite journal | vauthors = Saxena A, Wong LH, Kalitsis P, Earle E, Shaffer LG, Choo KH | title = Poly(ADP-ribose) polymerase 2 localizes to mammalian active centromeres and interacts with PARP-1, Cenpa, Cenpb and Bub3, but not Cenpc | journal = Human Molecular Genetics | volume = 11 | issue = 19 | pages = 2319–29 | date = September 2002 | pmid = 12217960 | doi = 10.1093/hmg/11.19.2319 }}
* {{cite journal | vauthors = Baek WK, Park JW, Lim JH, Suh SI, Suh MH, Gabrielson E, Kwon TK | title = Molecular cloning and characterization of the human budding uninhibited by benomyl (BUB3) promoter | journal = Gene | volume = 295 | issue = 1 | pages = 117–23 | date = July 2002 | pmid = 12242018 | doi = 10.1016/S0378-1119(02)00827-2 }}
* {{cite journal | vauthors = Liu L, Amy V, Liu G, McKeehan WL | title = Novel complex integrating mitochondria and the microtubular cytoskeleton with chromosome remodeling and tumor suppressor RASSF1 deduced by in silico homology analysis, interaction cloning in yeast, and colocalization in cultured cells | journal = In Vitro Cellular & Developmental Biology. Animal | volume = 38 | issue = 10 | pages = 582–94 | year = 2003 | pmid = 12762840 | pmc = 3225227 | doi = 10.1290/1543-706X(2002)38<582:NCIMAT>2.0.CO;2 | title-link = microtubule }}
* {{cite journal | vauthors = Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP | title = Large-scale characterization of HeLa cell nuclear phosphoproteins | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 33 | pages = 12130–5 | date = August 2004 | pmid = 15302935 | pmc = 514446 | doi = 10.1073/pnas.0404720101 | bibcode = 2004PNAS..10112130B }}
* {{cite journal | vauthors = Yoon YM, Baek KH, Jeong SJ, Shin HJ, Ha GH, Jeon AH, Hwang SG, Chun JS, Lee CW | title = WD repeat-containing mitotic checkpoint proteins act as transcriptional repressors during interphase | journal = FEBS Letters | volume = 575 | issue = 1-3 | pages = 23–9 | date = September 2004 | pmid = 15388328 | doi = 10.1016/j.febslet.2004.07.089 }}
* {{cite journal | vauthors = Tang Z, Shu H, Oncel D, Chen S, Yu H | title = Phosphorylation of Cdc20 by Bub1 provides a catalytic mechanism for APC/C inhibition by the spindle checkpoint | journal = Molecular Cell | volume = 16 | issue = 3 | pages = 387–97 | date = November 2004 | pmid = 15525512 | doi = 10.1016/j.molcel.2004.09.031 }}
* {{cite journal | vauthors = Andersen JS, Lam YW, Leung AK, Ong SE, Lyon CE, Lamond AI, Mann M | title = Nucleolar proteome dynamics | journal = Nature | volume = 433 | issue = 7021 | pages = 77–83 | date = January 2005 | pmid = 15635413 | doi = 10.1038/nature03207 | bibcode = 2005Natur.433...77A }}
* {{cite journal | vauthors = Mendoza S, David H, Gaylord GM, Miller CW | title = Allelic loss at 10q26 in osteosarcoma in the region of the BUB3 and FGFR2 genes | journal = Cancer Genetics and Cytogenetics | volume = 158 | issue = 2 | pages = 142–7 | date = April 2005 | pmid = 15796961 | doi = 10.1016/j.cancergencyto.2004.08.035 }}
* {{cite journal | vauthors = Lo KW, Kogoy JM, Pfister KK | title = The DYNLT3 light chain directly links cytoplasmic dynein to a spindle checkpoint protein, Bub3 | journal = The Journal of Biological Chemistry | volume = 282 | issue = 15 | pages = 11205–12 | date = April 2007 | pmid = 17289665 | doi = 10.1074/jbc.M611279200 }}
{{refend}}
 
== External links ==
* {{UCSC gene info|BUB3}}
* {{UCSC gene info|BUB3}}
==Further reading==
{{refbegin|35em}}
*{{cite journal  | vauthors=Cahill DP, da Costa LT, Carson-Walter EB |title=Characterization of MAD2B and other mitotic spindle checkpoint genes |journal=Genomics |volume=58 |issue= 2 |pages= 181–7 |year= 1999 |pmid= 10366450 |doi= 10.1006/geno.1999.5831 |display-authors=etal}}
*{{cite journal  | vauthors=Kwon TK, Hawkins AL, Griffin CA, Gabrielson E |title=Assignment of BUB3 to human chromosome band 10q26 by in situ hybridization |journal=Cytogenet. Cell Genet. |volume=88 |issue= 3–4 |pages= 202–3 |year= 2000 |pmid= 10828586 |doi=10.1159/000015547  }}
*{{cite journal  | vauthors=Saffery R, Irvine DV, Griffiths B |title=Components of the human spindle checkpoint control mechanism localize specifically to the active centromere on dicentric chromosomes |journal=Hum. Genet. |volume=107 |issue= 4 |pages= 376–84 |year= 2001 |pmid= 11129339 |doi=10.1007/s004390000386  |display-authors=etal}}
*{{cite journal  | vauthors=Kaplan KB, Burds AA, Swedlow JR |title=A role for the Adenomatous Polyposis Coli protein in chromosome segregation |journal=Nat. Cell Biol. |volume=3 |issue= 4 |pages= 429–32 |year= 2001 |pmid= 11283619 |doi= 10.1038/35070123 |display-authors=etal}}
*{{cite journal  | vauthors=Sudakin V, Chan GK, Yen TJ |title=Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2 |journal=J. Cell Biol. |volume=154 |issue= 5 |pages= 925–36 |year= 2001 |pmid= 11535616 |doi= 10.1083/jcb.200102093  | pmc=2196190 }}
*{{cite journal  | vauthors=Saxena A, Saffery R, Wong LH |title=Centromere proteins Cenpa, Cenpb, and Bub3 interact with poly(ADP-ribose) polymerase-1 protein and are poly(ADP-ribosyl)ated |journal=J. Biol. Chem. |volume=277 |issue= 30 |pages= 26921–6 |year= 2002 |pmid= 12011073 |doi= 10.1074/jbc.M200620200 |display-authors=etal}}
*{{cite journal  | vauthors=Saxena A, Wong LH, Kalitsis P |title=Poly(ADP-ribose) polymerase 2 localizes to mammalian active centromeres and interacts with PARP-1, Cenpa, Cenpb and Bub3, but not Cenpc |journal=Hum. Mol. Genet. |volume=11 |issue= 19 |pages= 2319–29 |year= 2003 |pmid= 12217960 |doi=10.1093/hmg/11.19.2319  |display-authors=etal}}
*{{cite journal  | vauthors=Baek WK, Park JW, Lim JH |title=Molecular cloning and characterization of the human budding uninhibited by benomyl (BUB3) promoter |journal=Gene |volume=295 |issue= 1 |pages= 117–23 |year= 2003 |pmid= 12242018 |doi=10.1016/S0378-1119(02)00827-2  |display-authors=etal}}
*{{cite journal  | vauthors=Strausberg RL, Feingold EA, Grouse LH |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899  | pmc=139241 |display-authors=etal}}
*{{cite journal  | vauthors=Liu L, Amy V, Liu G, McKeehan WL |title=Novel complex integrating mitochondria and the microtubular cytoskeleton with chromosome remodeling and tumor suppressor RASSF1 deduced by in silico homology analysis, interaction cloning in yeast, and colocalization in cultured cells |journal=In Vitro Cell. Dev. Biol. Anim. |volume=38 |issue= 10 |pages= 582–94 |year= 2003 |pmid= 12762840 |doi=10.1290/1543-706X(2002)38<582:NCIMAT>2.0.CO;2 |pmc=3225227}}
*{{cite journal  | vauthors=Beausoleil SA, Jedrychowski M, Schwartz D |title=Large-scale characterization of HeLa cell nuclear phosphoproteins |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=101 |issue= 33 |pages= 12130–5 |year= 2004 |pmid= 15302935 |doi= 10.1073/pnas.0404720101  | pmc=514446 |display-authors=etal}}
*{{cite journal  | vauthors=Yoon YM, Baek KH, Jeong SJ |title=WD repeat-containing mitotic checkpoint proteins act as transcriptional repressors during interphase |journal=FEBS Lett. |volume=575 |issue= 1–3 |pages= 23–9 |year= 2004 |pmid= 15388328 |doi= 10.1016/j.febslet.2004.07.089 |display-authors=etal}}
*{{cite journal  | vauthors=Gerhard DS, Wagner L, Feingold EA |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504  | pmc=528928 |display-authors=etal}}
*{{cite journal  | vauthors=Tang Z, Shu H, Oncel D |title=Phosphorylation of Cdc20 by Bub1 provides a catalytic mechanism for APC/C inhibition by the spindle checkpoint |journal=Mol. Cell |volume=16 |issue= 3 |pages= 387–97 |year= 2004 |pmid= 15525512 |doi= 10.1016/j.molcel.2004.09.031 |display-authors=etal}}
*{{cite journal  | vauthors=Andersen JS, Lam YW, Leung AK |title=Nucleolar proteome dynamics |journal=Nature |volume=433 |issue= 7021 |pages= 77–83 |year= 2005 |pmid= 15635413 |doi= 10.1038/nature03207 |display-authors=etal}}
*{{cite journal  | vauthors=Mendoza S, David H, Gaylord GM, Miller CW |title=Allelic loss at 10q26 in osteosarcoma in the region of the BUB3 and FGFR2 genes |journal=Cancer Genet. Cytogenet. |volume=158 |issue= 2 |pages= 142–7 |year= 2005 |pmid= 15796961 |doi= 10.1016/j.cancergencyto.2004.08.035 }}
*{{cite journal  | vauthors=Rual JF, Venkatesan K, Hao T |title=Towards a proteome-scale map of the human protein-protein interaction network |journal=Nature |volume=437 |issue= 7062 |pages= 1173–8 |year= 2005 |pmid= 16189514 |doi= 10.1038/nature04209 |display-authors=etal}}
*{{cite journal  | vauthors=Lo KW, Kogoy JM, Pfister KK |title=The DYNLT3 light chain directly links cytoplasmic dynein to a spindle checkpoint protein, Bub3 |journal=J. Biol. Chem. |volume=282 |issue= 15 |pages= 11205–12 |year= 2007 |pmid= 17289665 |doi= 10.1074/jbc.M611279200 }}
{{refend}}


{{DEFAULTSORT:Bub3}}
{{DEFAULTSORT:Bub3}}


[[Category:Proteins]]
[[Category:Proteins]]

Latest revision as of 11:47, 8 January 2019

VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

n/a

n/a

Ensembl

n/a

n/a

UniProt

n/a

n/a

RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Mitotic checkpoint protein BUB3 is a protein that in humans is encoded by the BUB3 gene.[1][2]

Bub3 is a protein involved with the regulation of the Spindle Assembly Checkpoint (SAC); though BUB3 is non-essential in yeast, it is essential in higher eukaryotes. As one of the checkpoint proteins, Bub3 delays the irreversible onset of anaphase through direction of kinetochore localization during prometaphase[1] to achieve biorentation. In directing the kinetochore-microtubule interaction, this ensures the proper (and consequenctly, bioriented) attachment of the chromosomes prior to anaphase. Bub3 and its related proteins that form the Spindle Assembly Checkpoint (SAC) inhibit the action of the Anaphase Promoting Complex (APC), preventing early anaphase entry and mitotic exit; this serves as a mechanism for the fidelity of chromosomal segregation.[3]

Function

Bub3 is a crucial component in the formation of the mitotic spindle assembly complex, which forms a complex with other important proteins.[4] For correct segregation of the cells it is necessary for all mitotic spindles to attach correctly to the kinetochore of each chromosome. This is controlled by the mitotic spindle checkpoint complex which operates as a feedback-response.[4] If there is a signal of a defect in the attachment, mitosis will be stopped to ensure that all chromosomes have an amphitelic binding to spindles. After the error is corrected, the cell will proceed to anaphase. The complex of proteins which regulate the cell arrest are BUB1, BUB2, BUB3 (this protein), Mad1, Mad2, Mad3 and MPS1.[4]

Role in the spindle assembly checkpoint

At unattached kinetochores, a complex consisting of BubR1, Bub3, and Cdc20 interact with the Mad2-Cdc20 complex to inhibit the APC, thus inhibiting the formation of active APCCdc20.[5][6] Bub3 binds constitutively to BubR1; in this arrangement, Bub3 acts as a key component of the SAC in the formation of an inhibitory complex.[7] Securin and cyclin B are also stabilized before the anaphase transition by the unattached kinetochores.[8] The stabilization of cyclin and securin prevent the degradation that would lead to the irreversible and fast separation of the sister chromatids.

The formation of these “inhibitory complexes” and steps feed into a ‘wait’ signal before activation of separase; at the stage prior to anaphase, securin inhibits the activity of separase and maintains the cohesion complex.[3]

Structure

The crystal structure of Bub3 indicates a protein of the seven-bladed beta-propeller structure with the presence of WD40 repeats, with each blade formed by four anti-parallel beta sheet strands that have been organized around a tapered channel. Mutation data suggest several important surfaces of interaction for the formation of the SAC, particularly the conserved tryptophans (in blades 1 and 3) and the conserved VAVE sequences in blade 5.

Rae1 (an mRNA export factor), another member of the WD40 protein family, shows high sequence conservation with that of Bub3. Both bind to Gle2p-binding-sequence (GLEBS) motifs; while Bub3 specifically binds Mad3 and Bub1, Rae1 has more promiscuous binding as it binds both the nuclear pore complex and Bub1. This indicates a similarity in interaction of Bub3 and Rae1 with Bub1.[9]

Interactions

BUB3 has been shown to interact with BUB1B,[1][10][11] HDAC1[12] and Histone deacetylase 2.[12]

Bub3 has been shown to form complexes with Mad1-Bub1 and with Cdc20 (the interaction of which does not require intact kinetochores). Additionally, it has been shown to bind Mad2 and Mad3.[7][13]

Bub3 directs the localization of Bub1 at the kinetochore in order to activate the SAC.[1] In both Saccharomyces cerevisiae and metazoans, Bub3 has been show to bind BubR1 and Bub1.[3]

The components that are essential for the spindle assembly checkpoint in yeast have been determined to be Bub1, Bub3, Mad1, Mad2, Mad3, and the increasingly important Mps1 (a protein kinase).

Regulation

When the SAC is activated, the production of the Bub3-Cdc20 complex is activated. After kinetochore attachment is complete, the spindle checkpoint complexes (including the BubR1-Bub3) experience a decrease in concentration.[14][15]

Bub3 also acts as a regulator in that it affects binding of Mad3 to Mad2.[7]

Structural and sequence analysis indicated the existence of three conserved regions that are referred to as WD40 repeats. Mutation of one of these motifs has indicated an impaired ability of Bub3 to interact with Mad2, Mad3, and Cdc20. The structural data suggested that Bub3 acts as a platform that mediates the interaction of SAC protein complexes.[7][9]

Clinical significance

BUB3 forms a complex with BUB1 (BUB1/BUB3 complex) to inhibit the anaphase-promoting complex or cyclosome (APC/C) as soon as the spindle-assembly checkpoint is activated. BUB3 also phosphorylates:

  • CDC20 (activator) and thereby inhibits the ubiquitin ligase activity of APC/C.
  • MAD1L1, which usually interacts with BUB1 and BUBR1, and in turn the BUB1/BUB3 complex interacts with MAD1L1.

Another function of BUB3 is to promote correct kinetochore-microtubule (K-MT) attachments when the spindle-assembly checkpoint is active. It plays a role in the localization of kinetochore of BUB1.

BUB3 serves in oocyte meiosis as the regulator of chromosome segregation.

Defects in BUB3 in the cell cycle can contribute to the following diseases:[4]

  • hepatocellular carcinoma
  • gastric cancer
  • breast cancer
  • cervical cancer
  • adenomatous polyposis
  • osteosarcoma familial breast cancer
  • glioblastoma cervicitis
  • lung cancer carcinoma
  • Coli polyposis

References

  1. ↑ 1.0 1.1 1.2 1.3 Taylor SS, Ha E, McKeon F (July 1998). "The human homologue of Bub3 is required for kinetochore localization of Bub1 and a Mad3/Bub1-related protein kinase". The Journal of Cell Biology. 142 (1): 1–11. doi:10.1083/jcb.142.1.1. PMC 2133037. PMID 9660858.
  2. ↑ "Entrez Gene: BUB3 BUB3 budding uninhibited by benzimidazoles 3 homolog (yeast)".
  3. ↑ 3.0 3.1 3.2 Morgan, David O (2007). The cell cycle: principles of control. London: Published by New Science Press in association with Oxford University Press. ISBN 978-0-87893-508-6.
  4. ↑ 4.0 4.1 4.2 4.3 Kalitsis P, Earle E, Fowler KJ, Choo KH (September 2000). "Bub3 gene disruption in mice reveals essential mitotic spindle checkpoint function during early embryogenesis". Genes & Development. 14 (18): 2277–82. doi:10.1101/gad.827500. PMC 316933. PMID 10995385.
  5. ↑ * Eytan E, Braunstein I, Ganoth D, Teichner A, Hittle JC, Yen TJ, Hershko A (July 2008). "Two different mitotic checkpoint inhibitors of the anaphase-promoting complex/cyclosome antagonize the action of the activator Cdc20". Proceedings of the National Academy of Sciences of the United States of America. 105 (27): 9181–5. Bibcode:2008PNAS..105.9181E. doi:10.1073/pnas.0804069105. PMC 2453698. PMID 18591651.
  6. ↑ * Fang G, Yu H & Kirschner MW (August 1998). "Direct binding of CDC20 protein family members activates the anaphase-promoting complex in mitosis and G1". Molecular Cell. 2 (2): 163–71. doi:10.1016/S1097-2765(00)80126-4. PMID 9734353.
  7. ↑ 7.0 7.1 7.2 7.3 * Fraschini R, Beretta A, Sironi L, Musacchio A, Lucchini G, Piatti S (December 2001). "Bub3 interaction with Mad2, Mad3 and Cdc20 is mediated by WD40 repeats and does not require intact kinetochores". The EMBO Journal. 20 (23): 6648–59. doi:10.1093/emboj/20.23.6648. PMC 125326. PMID 11726501.
  8. ↑ * Li M, Li S, Yuan J, Wang ZB, Sun SC, Schatten H, Sun QY (November 2009). Jin D, ed. "Bub3 is a spindle assembly checkpoint protein regulating chromosome segregation during mouse oocyte meiosis". PloS One. 4 (11): e7701. Bibcode:2009PLoSO...4.7701L. doi:10.1371/journal.pone.0007701. PMC 2765619. PMID 19888327.
  9. ↑ 9.0 9.1 * Larsen NA, Harrison SC (December 2004). "Crystal structure of the spindle assembly checkpoint protein Bub3". Journal of Molecular Biology. 344 (4): 885–92. doi:10.1016/j.jmb.2004.09.094. PMID 15544799.
  10. ↑ * Sudakin V, Chan GK, Yen TJ (September 2001). "Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2". The Journal of Cell Biology. 154 (5): 925–36. doi:10.1083/jcb.200102093. PMC 2196190. PMID 11535616.
  11. ↑ * Cayrol C, Cougoule C, Wright M (November 2002). "The beta2-adaptin clathrin adaptor interacts with the mitotic checkpoint kinase BubR1". Biochemical and Biophysical Research Communications. 298 (5): 720–30. doi:10.1016/S0006-291X(02)02522-6. PMID 12419313.
  12. ↑ 12.0 12.1 * Yoon YM, Baek KH, Jeong SJ, Shin HJ, Ha GH, Jeon AH, Hwang SG, Chun JS, Lee CW (September 2004). "WD repeat-containing mitotic checkpoint proteins act as transcriptional repressors during interphase". FEBS Letters. 575 (1–3): 23–9. doi:10.1016/j.febslet.2004.07.089. PMID 15388328.
  13. ↑ * Logarinho E, Bousbaa H (June 2008). "Kinetochore-microtubule interactions "in check" by Bub1, Bub3 and BubR1: The dual task of attaching and signalling". Cell Cycle. 7 (12): 1763–8. doi:10.4161/cc.7.12.6180. PMID 18594200.
  14. ↑ * Yu H (December 2002). "Regulation of APC-Cdc20 by the spindle checkpoint". Current Opinion in Cell Biology. 14 (6): 706–14. doi:10.1016/S0955-0674(02)00382-4. PMID 12473343.
  15. ↑ * Doncic A, Ben-Jacob E, Einav S, Barkai N (August 2009). Khanin R, ed. "Reverse engineering of the spindle assembly checkpoint". PloS One. 4 (8): e6495. Bibcode:2009PLoSO...4.6495D. doi:10.1371/journal.pone.0006495. PMC 2714964. PMID 19652707.

Further reading

External links

Retrieved from "https://www.wikidoc.org/index.php?title=BUB3&oldid=1541891"