StAR-related lipid transfer domain protein 13 (STARD13) also known as deleted in liver cancer 2 protein (DLC-2) is a protein that in humans is encoded by the STARD13gene and a member of the DLC family of proteins.[1][2]
STARD13 serves as a Rho GTPase-activating protein (GAP), a type of protein that regulates members of the Rho family of GTPases.[3] It selectively activates RhoA and CDC42 and suppresses cell growth by inhibiting actin stress fiber assembly.[3]
The protein consists of an N-terminal sterile alpha motif (SAM) domain,[4] a serine-rich domain, a RhoGAP domain and at the C-terminus, a StAR-related lipid-transfer domain (START).
Tissue distribution and pathology
The protein was identified in part through its differential expression in cancers. A low level of STARD13 was observed in less differentiated hepatocellular carcinoma tissue with higher RhoA expression. A small patient study finds that the absence of STARD13 in hepatocellular carcinomas correlates with higher levels of RhoA and a poorer prognosis than patients with carcinomas that were STARD13-positive.[5]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[9][16] Twenty four tests were carried out on mutant mice and two significant abnormalities were observed. Female homozygous mutants had an increased susceptibility to Citrobacter infection and displayed a decreased hematocrit and hemoglobin content.[9]
Another study of mice lacking STARD13, found it may promote blood vessel formation (angiogenesis), especially by tumor cells.[17] The promotion of angiogenesis with the loss of STARD13 occurs through the actions of RhoA.[17]
References
↑Couch FJ, Rommens JM, Neuhausen SL, Bélanger C, Dumont M, Abel K, Bell R, Berry S, Bogden R, Cannon-Albright L, Farid L, Frye C, Hattier T, Janecki T, Jiang P, Kehrer R, Leblanc JF, McArthur-Morrison J, Meney D, Miki Y, Peng Y, Samson C, Schroeder M, Snyder SC, Simard J (August 1996). "Generation of an integrated transcription map of the BRCA2 region on chromosome 13q12-q13". Genomics. 36 (1): 86–99. doi:10.1006/geno.1996.0428. PMID8812419.
↑ 3.03.1Ching YP, Wong CM, Chan SF, Leung TH, Ng DC, Jin DY, Ng IO (March 2003). "Deleted in liver cancer (DLC) 2 encodes a RhoGAP protein with growth suppressor function and is underexpressed in hepatocellular carcinoma". The Journal of Biological Chemistry. 278 (12): 10824–30. doi:10.1074/jbc.M208310200. PMID12531887.
↑Li, Hongyan; Fung, King-Leung; Jin, Dong-Yan; Chung, Stephen S. M.; Ching, Yick-Pang; Ng, Irene Oi-lin; Sze, Kong-Hung; Ko, Ben C. B.; Sun, Hongzhe (2007-06-01). "Solution structures, dynamics, and lipid-binding of the sterile alpha-motif domain of the deleted in liver cancer 2". Proteins. 67 (4): 1154–1166. doi:10.1002/prot.21361. ISSN1097-0134. PMID17380510.
↑ 9.09.19.2Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88 (S248). doi:10.1111/j.1755-3768.2010.4142.x.
Ching YP, Wong CM, Chan SF, Leung TH, Ng DC, Jin DY, Ng IO (March 2003). "Deleted in liver cancer (DLC) 2 encodes a RhoGAP protein with growth suppressor function and is underexpressed in hepatocellular carcinoma". The Journal of Biological Chemistry. 278 (12): 10824–30. doi:10.1074/jbc.M208310200. PMID12531887.
Nagaraja GM, Kandpal RP (January 2004). "Chromosome 13q12 encoded Rho GTPase activating protein suppresses growth of breast carcinoma cells, and yeast two-hybrid screen shows its interaction with several proteins". Biochemical and Biophysical Research Communications. 313 (3): 654–65. doi:10.1016/j.bbrc.2003.12.001. PMID14697242.
