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{{Infobox_gene}}
'''Cyclin-dependent kinase inhibitor 1C (p57, Kip2)''', also known as '''CDKN1C''', is a [[protein]] which in humans is encoded by the ''CDKN1C''  [[genomic imprinting|imprinted]] [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: CDKN1C cyclin-dependent kinase inhibitor 1C (p57, Kip2)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1028| accessdate = }}</ref>


<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
== Function ==
{{PBB_Controls
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
Cyclin-dependent kinase inhibitor 1C is a tight-binding inhibitor of several G1 cyclin/Cdk complexes and a negative regulator of cell proliferation. Mutations of CDKN1C are implicated in sporadic cancers and [[Beckwith-Wiedemann syndrome]] suggesting that it is a tumor suppressor candidate.<ref name="entrez" />
{{GNF_Protein_box
| image = 
| image_source = 
| PDB =
| Name = Cyclin-dependent kinase inhibitor 1C (p57, Kip2)
| HGNCid = 1786
| Symbol = CDKN1C
| AltSymbols =; BWCR; BWS; KIP2; WBS; p57
| OMIM = 600856
| ECnumber = 
| Homologene = 58
| MGIid = 104564
| GeneAtlas_image1 = PBB_GE_CDKN1C_213348_at_tn.png
| GeneAtlas_image2 = PBB_GE_CDKN1C_213182_x_at_tn.png
| GeneAtlas_image3 = PBB_GE_CDKN1C_216894_x_at_tn.png
| Function = {{GNF_GO|id=GO:0004861 |text = cyclin-dependent protein kinase inhibitor activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}}
| Process = {{GNF_GO|id=GO:0000079 |text = regulation of cyclin-dependent protein kinase activity}} {{GNF_GO|id=GO:0000080 |text = G1 phase of mitotic cell cycle}} {{GNF_GO|id=GO:0000122 |text = negative regulation of transcription from RNA polymerase II promoter}} {{GNF_GO|id=GO:0007049 |text = cell cycle}} {{GNF_GO|id=GO:0007050 |text = cell cycle arrest}} {{GNF_GO|id=GO:0008285 |text = negative regulation of cell proliferation}} {{GNF_GO|id=GO:0042551 |text = neuron maturation}}
  | Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 1028
    | Hs_Ensembl = ENSG00000129757
    | Hs_RefseqProtein = NP_000067
    | Hs_RefseqmRNA = NM_000076
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 11
    | Hs_GenLoc_start = 2861019
    | Hs_GenLoc_end = 2863577
    | Hs_Uniprot = P49918
    | Mm_EntrezGene = 12577
    | Mm_Ensembl = ENSMUSG00000037664
    | Mm_RefseqmRNA = NM_009876
    | Mm_RefseqProtein = NP_034006
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 7
    | Mm_GenLoc_start = 143267730
    | Mm_GenLoc_end = 143270386
    | Mm_Uniprot = Q791X1
  }}
}}
'''Cyclin-dependent kinase inhibitor 1C (p57, Kip2)''', also known as '''CDKN1C''', is an [[genomic imprinting|imprinted]] human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: CDKN1C cyclin-dependent kinase inhibitor 1C (p57, Kip2)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1028| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
CDKN1C is a [[tumor suppressor]] human [[gene]] on [[chromosome 11]] (11p15) and belongs to the ''cip/kip'' gene family. It encodes a [[cell cycle]] inhibitor that binds to G1 [[cyclin-CDK]] complexes.<ref name="pmid7729684">{{cite journal | vauthors = Matsuoka S, Edwards MC, Bai C, Parker S, Zhang P, Baldini A, Harper JW, Elledge SJ | title = p57KIP2, a structurally distinct member of the p21CIP1 Cdk inhibitor family, is a candidate tumor suppressor gene | journal = Genes & Development | volume = 9 | issue = 6 | pages = 650–62 | date = Mar 1995 | pmid = 7729684 | doi = 10.1101/gad.9.6.650 }}</ref> Thus p57KIP2 causes arrest of the cell cycle in [[G1 phase]].
{{PBB_Summary
| section_title =
| summary_text = Cyclin-dependent kinase inhibitor 1C is a tight-binding inhibitor of several G1 cyclin/Cdk complexes and a negative regulator of cell proliferation.  Mutations of CDKN1C are implicated in sporadic cancers and Beckwith-Wiedemann syndorome suggesting that it is a tumor suppressor candidate.<ref name="entrez">{{cite web | title = Entrez Gene: CDKN1C cyclin-dependent kinase inhibitor 1C (p57, Kip2)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1028| accessdate = }}</ref>
}}


==References==
== Clinical significance ==
 
A [[mutation]] of this gene may lead to loss of control over the cell cycle leading to uncontrolled cellular proliferation. p57KIP2 has been associated with [[Beckwith-Wiedemann syndrome]] (BWS) which is characterized by increased risk of tumor formation in childhood.<ref name="pmid">{{cite journal | vauthors = Hatada I, Nabetani A, Morisaki H, Xin Z, Ohishi S, Tonoki H, Niikawa N, Inoue M, Komoto Y, Okada A, Steichen E, Ohashi H, Fukushima Y, Nakayama M, Mukai T | title = New p57KIP2 mutations in Beckwith-Wiedemann syndrome | journal = Human Genetics | volume = 100 | issue = 5-6 | pages = 681–3 | date = Oct 1997 | pmid = 9341892 | doi = 10.1007/s004390050573 }}</ref> Loss-of-function mutations in this gene have also been shown associated to the [[IMAGe syndrome]] (Intrauterine growth restriction, Metaphyseal dysplasia, Adrenal hypoplasia congenita, and Genital anomalies).<ref name="doi.10.1038/ng.2336">{{cite journal | vauthors = Riccio A, Cubellis MV | title = Gain of function in CDKN1C | journal = Nature Genetics | volume = 44 | issue = 7 | pages = 737–8 | date = Jul 2012 | pmid = 22735584 | doi = 10.1038/ng.2336 }}</ref>  Complete hydatidiform moles consist only of paternal DNA, and thus the cells lack p57 expression as the gene is paternally imprinted (silenced). Immuohistochemical stains for p57 can aid with the diagnosis of hydatidiform moles <ref>{{Cite journal|last = LeGallo|first = Robin D.|last2 = Stelow|first2 = Edward B.|last3 = Ramirez|first3 = Nilsa C.|last4 = Atkins|first4 = Kristen A.|date = 2008-05-01|title = Diagnosis of hydatidiform moles using p57 immunohistochemistry and HER2 fluorescent in situ hybridization|journal = American Journal of Clinical Pathology|volume = 129|issue = 5|pages = 749–755|doi = 10.1309/7XRL378C22W7APBT|issn = 0002-9173|pmid = 18426735}}</ref>
 
== Interactions ==
 
Cyclin-dependent kinase inhibitor 1C has been shown to [[Protein-protein interaction|interact]] with:
* [[LIMK1]],<ref name = pmid14530263>{{cite journal | vauthors = Yokoo T, Toyoshima H, Miura M, Wang Y, Iida KT, Suzuki H, Sone H, Shimano H, Gotoda T, Nishimori S, Tanaka K, Yamada N | title = p57Kip2 regulates actin dynamics by binding and translocating LIM-kinase 1 to the nucleus | journal = The Journal of Biological Chemistry | volume = 278 | issue = 52 | pages = 52919–23 | date = Dec 2003 | pmid = 14530263 | doi = 10.1074/jbc.M309334200 }}</ref>
* [[MYBL2]],<ref name = pmid12947099>{{cite journal | vauthors = Joaquin M, Watson RJ | title = The cell cycle-regulated B-Myb transcription factor overcomes cyclin-dependent kinase inhibitory activity of p57(KIP2) by interacting with its cyclin-binding domain | journal = The Journal of Biological Chemistry | volume = 278 | issue = 45 | pages = 44255–64 | date = Nov 2003 | pmid = 12947099 | doi = 10.1074/jbc.M308953200 }}</ref>
* [[MyoD]],<ref name = pmid10764802>{{cite journal | vauthors = Reynaud EG, Leibovitch MP, Tintignac LA, Pelpel K, Guillier M, Leibovitch SA | title = Stabilization of MyoD by direct binding to p57(Kip2) | journal = The Journal of Biological Chemistry | volume = 275 | issue = 25 | pages = 18767–76 | date = Jun 2000 | pmid = 10764802 | doi = 10.1074/jbc.M907412199 }}</ref>  and
* [[PCNA]].<ref name = pmid9465025>{{cite journal | vauthors = Watanabe H, Pan ZQ, Schreiber-Agus N, DePinho RA, Hurwitz J, Xiong Y | title = Suppression of cell transformation by the cyclin-dependent kinase inhibitor p57KIP2 requires binding to proliferating cell nuclear antigen | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 95 | issue = 4 | pages = 1392–7 | date = Feb 1998 | pmid = 9465025 | pmc = 19016 | doi =  10.1073/pnas.95.4.1392}}</ref>
 
== References ==
{{reflist}}
{{reflist}}
==Further reading==
 
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Seizinger BR | title = Genes associated with tumor suppression and growth control in the human nervous system | journal = Cancer Metastasis Reviews | volume = 10 | issue = 4 | pages = 281–7 | date = Dec 1991 | pmid = 1786629 | doi = 10.1007/BF00554790 }}
| citations =
* {{cite journal | vauthors = Lee MH, Reynisdóttir I, Massagué J | title = Cloning of p57KIP2, a cyclin-dependent kinase inhibitor with unique domain structure and tissue distribution | journal = Genes & Development | volume = 9 | issue = 6 | pages = 639–49 | date = Mar 1995 | pmid = 7729683 | doi = 10.1101/gad.9.6.639 }}
*{{cite journal | author=Seizinger BR |title=Genes associated with tumor suppression and growth control in the human nervous system. |journal=Cancer Metastasis Rev. |volume=10 |issue= 4 |pages= 281-7 |year= 1992 |pmid= 1786629 |doi= }}
* {{cite journal | vauthors = Matsuoka S, Edwards MC, Bai C, Parker S, Zhang P, Baldini A, Harper JW, Elledge SJ | title = p57KIP2, a structurally distinct member of the p21CIP1 Cdk inhibitor family, is a candidate tumor suppressor gene | journal = Genes & Development | volume = 9 | issue = 6 | pages = 650–62 | date = Mar 1995 | pmid = 7729684 | doi = 10.1101/gad.9.6.650 }}
*{{cite journal | author=Lee MH, Reynisdóttir I, Massagué J |title=Cloning of p57KIP2, a cyclin-dependent kinase inhibitor with unique domain structure and tissue distribution. |journal=Genes Dev. |volume=9 |issue= 6 |pages= 639-49 |year= 1995 |pmid= 7729683 |doi= }}
* {{cite journal | vauthors = Matsuoka S, Thompson JS, Edwards MC, Bartletta JM, Grundy P, Kalikin LM, Harper JW, Elledge SJ, Feinberg AP | title = Imprinting of the gene encoding a human cyclin-dependent kinase inhibitor, p57KIP2, on chromosome 11p15 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 93 | issue = 7 | pages = 3026–30 | date = Apr 1996 | pmid = 8610162 | pmc = 39755 | doi = 10.1073/pnas.93.7.3026 }}
*{{cite journal | author=Matsuoka S, Edwards MC, Bai C, ''et al.'' |title=p57KIP2, a structurally distinct member of the p21CIP1 Cdk inhibitor family, is a candidate tumor suppressor gene. |journal=Genes Dev. |volume=9 |issue= 6 |pages= 650-62 |year= 1995 |pmid= 7729684 |doi= }}
* {{cite journal | vauthors = Reid LH, Crider-Miller SJ, West A, Lee MH, Massagué J, Weissman BE | title = Genomic organization of the human p57KIP2 gene and its analysis in the G401 Wilms' tumor assay | journal = Cancer Research | volume = 56 | issue = 6 | pages = 1214–8 | date = Mar 1996 | pmid = 8640800 | doi =  }}
*{{cite journal | author=Matsuoka S, Thompson JS, Edwards MC, ''et al.'' |title=Imprinting of the gene encoding a human cyclin-dependent kinase inhibitor, p57KIP2, on chromosome 11p15. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=93 |issue= 7 |pages= 3026-30 |year= 1996 |pmid= 8610162 |doi= }}
* {{cite journal | vauthors = Tokino T, Urano T, Furuhata T, Matsushima M, Miyatsu T, Sasaki S, Nakamura Y | title = Characterization of the human p57KIP2 gene: alternative splicing, insertion/deletion polymorphisms in VNTR sequences in the coding region, and mutational analysis | journal = Human Genetics | volume = 97 | issue = 5 | pages = 625–31 | date = May 1996 | pmid = 8655143 | doi = 10.1007/BF02281873 }}
*{{cite journal  | author=Reid LH, Crider-Miller SJ, West A, ''et al.'' |title=Genomic organization of the human p57KIP2 gene and its analysis in the G401 Wilms' tumor assay. |journal=Cancer Res. |volume=56 |issue= 6 |pages= 1214-8 |year= 1996 |pmid= 8640800 |doi=  }}
* {{cite journal | vauthors = Hatada I, Ohashi H, Fukushima Y, Kaneko Y, Inoue M, Komoto Y, Okada A, Ohishi S, Nabetani A, Morisaki H, Nakayama M, Niikawa N, Mukai T | title = An imprinted gene p57KIP2 is mutated in Beckwith-Wiedemann syndrome | journal = Nature Genetics | volume = 14 | issue = 2 | pages = 171–3 | date = Oct 1996 | pmid = 8841187 | doi = 10.1038/ng1096-171 }}
*{{cite journal | author=Tokino T, Urano T, Furuhata T, ''et al.'' |title=Characterization of the human p57KIP2 gene: alternative splicing, insertion/deletion polymorphisms in VNTR sequences in the coding region, and mutational analysis. |journal=Hum. Genet. |volume=97 |issue= 5 |pages= 625-31 |year= 1996 |pmid= 8655143 |doi= }}
* {{cite journal | vauthors = Furuhata T, Tokino T, Urano T, Nakamura Y | title = Isolation of a novel GPI-anchored gene specifically regulated by p53; correlation between its expression and anti-cancer drug sensitivity | journal = Oncogene | volume = 13 | issue = 9 | pages = 1965–70 | date = Nov 1996 | pmid = 8934543 | doi =  }}
*{{cite journal | author=Hatada I, Ohashi H, Fukushima Y, ''et al.'' |title=An imprinted gene p57KIP2 is mutated in Beckwith-Wiedemann syndrome. |journal=Nat. Genet. |volume=14 |issue= 2 |pages= 171-3 |year= 1996 |pmid= 8841187 |doi= 10.1038/ng1096-171 }}
* {{cite journal | vauthors = LaBaer J, Garrett MD, Stevenson LF, Slingerland JM, Sandhu C, Chou HS, Fattaey A, Harlow E | title = New functional activities for the p21 family of CDK inhibitors | journal = Genes & Development | volume = 11 | issue = 7 | pages = 847–62 | date = Apr 1997 | pmid = 9106657 | doi = 10.1101/gad.11.7.847 }}
*{{cite journal | author=Furuhata T, Tokino T, Urano T, Nakamura Y |title=Isolation of a novel GPI-anchored gene specifically regulated by p53; correlation between its expression and anti-cancer drug sensitivity. |journal=Oncogene |volume=13 |issue= 9 |pages= 1965-70 |year= 1997 |pmid= 8934543 |doi=  }}
* {{cite journal | vauthors = Watanabe H, Pan ZQ, Schreiber-Agus N, DePinho RA, Hurwitz J, Xiong Y | title = Suppression of cell transformation by the cyclin-dependent kinase inhibitor p57KIP2 requires binding to proliferating cell nuclear antigen | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 95 | issue = 4 | pages = 1392–7 | date = Feb 1998 | pmid = 9465025 | pmc = 19016 | doi = 10.1073/pnas.95.4.1392 }}
*{{cite journal | author=LaBaer J, Garrett MD, Stevenson LF, ''et al.'' |title=New functional activities for the p21 family of CDK inhibitors. |journal=Genes Dev. |volume=11 |issue= 7 |pages= 847-62 |year= 1997 |pmid= 9106657 |doi= }}
* {{cite journal | vauthors = Bhuiyan ZA, Yatsuki H, Sasaguri T, Joh K, Soejima H, Zhu X, Hatada I, Morisaki H, Morisaki T, Mukai T | title = Functional analysis of the p57KIP2 gene mutation in Beckwith-Wiedemann syndrome | journal = Human Genetics | volume = 104 | issue = 3 | pages = 205–10 | date = Mar 1999 | pmid = 10323243 | doi = 10.1007/s004390050937 }}
*{{cite journal | author=Watanabe H, Pan ZQ, Schreiber-Agus N, ''et al.'' |title=Suppression of cell transformation by the cyclin-dependent kinase inhibitor p57KIP2 requires binding to proliferating cell nuclear antigen. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=95 |issue= 4 |pages= 1392-7 |year= 1998 |pmid= 9465025 |doi= }}
* {{cite journal | vauthors = Lam WW, Hatada I, Ohishi S, Mukai T, Joyce JA, Cole TR, Donnai D, Reik W, Schofield PN, Maher ER | title = Analysis of germline CDKN1C (p57KIP2) mutations in familial and sporadic Beckwith-Wiedemann syndrome (BWS) provides a novel genotype-phenotype correlation | journal = Journal of Medical Genetics | volume = 36 | issue = 7 | pages = 518–23 | date = Jul 1999 | pmid = 10424811 | pmc = 1734395 | doi = 10.1136/jmg.36.7.518 }}
*{{cite journal | author=Bhuiyan ZA, Yatsuki H, Sasaguri T, ''et al.'' |title=Functional analysis of the p57KIP2 gene mutation in Beckwith-Wiedemann syndrome. |journal=Hum. Genet. |volume=104 |issue= 3 |pages= 205-10 |year= 1999 |pmid= 10323243 |doi= }}
* {{cite journal | vauthors = Reynaud EG, Leibovitch MP, Tintignac LA, Pelpel K, Guillier M, Leibovitch SA | title = Stabilization of MyoD by direct binding to p57(Kip2) | journal = The Journal of Biological Chemistry | volume = 275 | issue = 25 | pages = 18767–76 | date = Jun 2000 | pmid = 10764802 | doi = 10.1074/jbc.M907412199 }}
*{{cite journal | author=Lam WW, Hatada I, Ohishi S, ''et al.'' |title=Analysis of germline CDKN1C (p57KIP2) mutations in familial and sporadic Beckwith-Wiedemann syndrome (BWS) provides a novel genotype-phenotype correlation. |journal=J. Med. Genet. |volume=36 |issue= 7 |pages= 518-23 |year= 1999 |pmid= 10424811 |doi= }}
* {{cite journal | vauthors = Fink JR, LeBien TW | title = Novel expression of cyclin-dependent kinase inhibitors in human B-cell precursors | journal = Experimental Hematology | volume = 29 | issue = 4 | pages = 490–8 | date = Apr 2001 | pmid = 11301189 | doi = 10.1016/S0301-472X(01)00619-1 }}
*{{cite journal | author=Reynaud EG, Leibovitch MP, Tintignac LA, ''et al.'' |title=Stabilization of MyoD by direct binding to p57(Kip2). |journal=J. Biol. Chem. |volume=275 |issue= 25 |pages= 18767-76 |year= 2000 |pmid= 10764802 |doi= 10.1074/jbc.M907412199 }}
* {{cite journal | vauthors = Kido K, Doerks A, Lochelt M, Flügel RM | title = Identification and functional characterization of an intragenic DNA binding site for the spumaretroviral trans-activator in the human p57Kip2 gene | journal = The Journal of Biological Chemistry | volume = 277 | issue = 14 | pages = 12032–9 | date = Apr 2002 | pmid = 11815601 | doi = 10.1074/jbc.M108747200 }}
*{{cite journal | author=Fink JR, LeBien TW |title=Novel expression of cyclin-dependent kinase inhibitors in human B-cell precursors. |journal=Exp. Hematol. |volume=29 |issue= 4 |pages= 490-8 |year= 2001 |pmid= 11301189 |doi= }}
* {{cite journal | vauthors = Balint E, Phillips AC, Kozlov S, Stewart CL, Vousden KH | title = Induction of p57(KIP2) expression by p73beta | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 6 | pages = 3529–34 | date = Mar 2002 | pmid = 11891335 | pmc = 122557 | doi = 10.1073/pnas.062491899 }}
*{{cite journal | author=Kido K, Doerks A, Lochelt M, Flügel RM |title=Identification and functional characterization of an intragenic DNA binding site for the spumaretroviral trans-activator in the human p57Kip2 gene. |journal=J. Biol. Chem. |volume=277 |issue= 14 |pages= 12032-9 |year= 2002 |pmid= 11815601 |doi= 10.1074/jbc.M108747200 }}
* {{cite journal | vauthors = Ito Y, Yoshida H, Nakano K, Kobayashi K, Yokozawa T, Hirai K, Matsuzuka F, Matsuura N, Kuma K, Miyauchi A | title = Expression of p57/Kip2 protein in normal and neoplastic thyroid tissues | journal = International Journal of Molecular Medicine | volume = 9 | issue = 4 | pages = 373–6 | date = Apr 2002 | pmid = 11891530 | doi = 10.3892/ijmm.9.4.373 }}
*{{cite journal | author=Blint E, Phillips AC, Kozlov S, ''et al.'' |title=Induction of p57(KIP2) expression by p73beta. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 6 |pages= 3529-34 |year= 2002 |pmid= 11891335 |doi= 10.1073/pnas.062491899 }}
* {{cite journal | vauthors = Kikuchi T, Toyota M, Itoh F, Suzuki H, Obata T, Yamamoto H, Kakiuchi H, Kusano M, Issa JP, Tokino T, Imai K | title = Inactivation of p57KIP2 by regional promoter hypermethylation and histone deacetylation in human tumors | journal = Oncogene | volume = 21 | issue = 17 | pages = 2741–9 | date = Apr 2002 | pmid = 11965547 | doi = 10.1038/sj.onc.1205376 }}
*{{cite journal | author=Ito Y, Yoshida H, Nakano K, ''et al.'' |title=Expression of p57/Kip2 protein in normal and neoplastic thyroid tissues. |journal=Int. J. Mol. Med. |volume=9 |issue= 4 |pages= 373-6 |year= 2002 |pmid= 11891530 |doi= }}
* {{cite journal | vauthors = Li Y, Nagai H, Ohno T, Yuge M, Hatano S, Ito E, Mori N, Saito H, Kinoshita T | title = Aberrant DNA methylation of p57(KIP2) gene in the promoter region in lymphoid malignancies of B-cell phenotype | journal = Blood | volume = 100 | issue = 7 | pages = 2572–7 | date = Oct 2002 | pmid = 12239171 | doi = 10.1182/blood-2001-11-0026 }}
*{{cite journal | author=Kikuchi T, Toyota M, Itoh F, ''et al.'' |title=Inactivation of p57KIP2 by regional promoter hypermethylation and histone deacetylation in human tumors. |journal=Oncogene |volume=21 |issue= 17 |pages= 2741-9 |year= 2002 |pmid= 11965547 |doi= 10.1038/sj.onc.1205376 }}
*{{cite journal  | author=Li Y, Nagai H, Ohno T, ''et al.'' |title=Aberrant DNA methylation of p57(KIP2) gene in the promoter region in lymphoid malignancies of B-cell phenotype. |journal=Blood |volume=100 |issue= 7 |pages= 2572-7 |year= 2002 |pmid= 12239171 |doi= 10.1182/blood-2001-11-0026 }}
}}
{{refend}}
{{refend}}


{{protein-stub}}
== External links ==
* [https://www.ncbi.nlm.nih.gov/books/NBK1394/  GeneReviews/NIH/NCBI/UW entry on Beckwith-Wiedemann Syndrome]
* {{UCSC genome browser|CDKN1C}}
* {{UCSC gene details|CDKN1C}}
 
{{Cell cycle proteins}}
{{Tumor suppressor genes}}


{{WH}}
[[Category:Cell cycle]]
{{WikiDoc Sources}}
[[Category:Tumor suppressor genes]]

Latest revision as of 12:23, 13 November 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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

Cyclin-dependent kinase inhibitor 1C (p57, Kip2), also known as CDKN1C, is a protein which in humans is encoded by the CDKN1C imprinted gene.[1]

Function

Cyclin-dependent kinase inhibitor 1C is a tight-binding inhibitor of several G1 cyclin/Cdk complexes and a negative regulator of cell proliferation. Mutations of CDKN1C are implicated in sporadic cancers and Beckwith-Wiedemann syndrome suggesting that it is a tumor suppressor candidate.[1]

CDKN1C is a tumor suppressor human gene on chromosome 11 (11p15) and belongs to the cip/kip gene family. It encodes a cell cycle inhibitor that binds to G1 cyclin-CDK complexes.[2] Thus p57KIP2 causes arrest of the cell cycle in G1 phase.

Clinical significance

A mutation of this gene may lead to loss of control over the cell cycle leading to uncontrolled cellular proliferation. p57KIP2 has been associated with Beckwith-Wiedemann syndrome (BWS) which is characterized by increased risk of tumor formation in childhood.[3] Loss-of-function mutations in this gene have also been shown associated to the IMAGe syndrome (Intrauterine growth restriction, Metaphyseal dysplasia, Adrenal hypoplasia congenita, and Genital anomalies).[4] Complete hydatidiform moles consist only of paternal DNA, and thus the cells lack p57 expression as the gene is paternally imprinted (silenced). Immuohistochemical stains for p57 can aid with the diagnosis of hydatidiform moles [5]

Interactions

Cyclin-dependent kinase inhibitor 1C has been shown to interact with:

References

  1. ↑ 1.0 1.1 "Entrez Gene: CDKN1C cyclin-dependent kinase inhibitor 1C (p57, Kip2)".
  2. ↑ Matsuoka S, Edwards MC, Bai C, Parker S, Zhang P, Baldini A, Harper JW, Elledge SJ (Mar 1995). "p57KIP2, a structurally distinct member of the p21CIP1 Cdk inhibitor family, is a candidate tumor suppressor gene". Genes & Development. 9 (6): 650–62. doi:10.1101/gad.9.6.650. PMID 7729684.
  3. ↑ Hatada I, Nabetani A, Morisaki H, Xin Z, Ohishi S, Tonoki H, Niikawa N, Inoue M, Komoto Y, Okada A, Steichen E, Ohashi H, Fukushima Y, Nakayama M, Mukai T (Oct 1997). "New p57KIP2 mutations in Beckwith-Wiedemann syndrome". Human Genetics. 100 (5–6): 681–3. doi:10.1007/s004390050573. PMID 9341892.
  4. ↑ Riccio A, Cubellis MV (Jul 2012). "Gain of function in CDKN1C". Nature Genetics. 44 (7): 737–8. doi:10.1038/ng.2336. PMID 22735584.
  5. ↑ LeGallo, Robin D.; Stelow, Edward B.; Ramirez, Nilsa C.; Atkins, Kristen A. (2008-05-01). "Diagnosis of hydatidiform moles using p57 immunohistochemistry and HER2 fluorescent in situ hybridization". American Journal of Clinical Pathology. 129 (5): 749–755. doi:10.1309/7XRL378C22W7APBT. ISSN 0002-9173. PMID 18426735.
  6. ↑ Yokoo T, Toyoshima H, Miura M, Wang Y, Iida KT, Suzuki H, Sone H, Shimano H, Gotoda T, Nishimori S, Tanaka K, Yamada N (Dec 2003). "p57Kip2 regulates actin dynamics by binding and translocating LIM-kinase 1 to the nucleus". The Journal of Biological Chemistry. 278 (52): 52919–23. doi:10.1074/jbc.M309334200. PMID 14530263.
  7. ↑ Joaquin M, Watson RJ (Nov 2003). "The cell cycle-regulated B-Myb transcription factor overcomes cyclin-dependent kinase inhibitory activity of p57(KIP2) by interacting with its cyclin-binding domain". The Journal of Biological Chemistry. 278 (45): 44255–64. doi:10.1074/jbc.M308953200. PMID 12947099.
  8. ↑ Reynaud EG, Leibovitch MP, Tintignac LA, Pelpel K, Guillier M, Leibovitch SA (Jun 2000). "Stabilization of MyoD by direct binding to p57(Kip2)". The Journal of Biological Chemistry. 275 (25): 18767–76. doi:10.1074/jbc.M907412199. PMID 10764802.
  9. ↑ Watanabe H, Pan ZQ, Schreiber-Agus N, DePinho RA, Hurwitz J, Xiong Y (Feb 1998). "Suppression of cell transformation by the cyclin-dependent kinase inhibitor p57KIP2 requires binding to proliferating cell nuclear antigen". Proceedings of the National Academy of Sciences of the United States of America. 95 (4): 1392–7. doi:10.1073/pnas.95.4.1392. PMC 19016. PMID 9465025.

Further reading

External links

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