Human CMTM2/CKLFSF2 enhances the ligand-induced transactivation of the androgen receptor  

作　　者：LIU DaZhen YIN CaiHua ZHANG YingMei TIAN LinJie LI Ting LI Dan MA DaLong GUO YingLu WANG Ying 

机构地区：[1]Department of Urology, First Hospital of Peking University, Beijing 100034, China [2]Department of Medical Immunology, School of Basic Medical Science, Peking University Health Science Center, Beijing 100083, China [3]Center for Human Disease Genomics, Peking University, Beijing 100083, China [4]Department of Urology, General Hospital of Tianjin Medical University, Tianjin 300052, China

出　　处：《Chinese Science Bulletin》2009年第6期1050-1057,共8页

基　　金：Supported by National High Technology Research and Development Program of China (Grant Nos. 2006AA02A305 and 2002BA711A01);National Natural Science Foundation of China (Grant Nos. 30271203 and 30671907)

摘　　要：CKLF (chemokine-like factor)-like MARVEL (MAL and related proteins for vesicle trafficking and mem-brane link domain) transmembrane domain containing (CMTM) is a novel gene family. One member of this family, CMTM2, also named chemokine-like factor superfamily 2 (CKLFSF2), is expressed highly in the testis and moderately in the prostate, marrow and peripheral blood cells. However, the function of human CMTM2 remains unknown. Here, we found that CMTM2 was upregulated in 5α-dihydrotestos- terone (DHT)-treated LNCaP cells. We investigated the relationship between CMTM2 and the androgen receptor. Our results showed that CMTM2 enhanced DHT-mediated androgen receptor (AR) transacti-vation and the expression of prostate specific antigen (PSA). We also observed that CMTM2 enhanced the AR protein level, which was reversed by silencing endogenous CMTM2 expression, which sug-gested that CMTM2 might play an important role in maintaining the AR protein level. We also found that CMTM2 suppressed Akt activation. A previous study showed that Akt could phosphorylate AR at Ser210 and Ser790 and lead to AR ubiquitylation and degradation as well as suppression of AR activity. Taken together, suppressing Akt activation and increasing the AR protein level might be one of the mechanisms for the CMTM2-mediated enhancement of AR transactivation.CKLF （chemokine-like factor）-Iike MARVEL （MAL and related proteins for vesicle trafficking and membrane link domain） transmembrane domain containing （CMTM） is a novel gene family. One member of this family, CMTM2, also named chemokine-like factor superfamily 2 （CKLFSF2）, is expressed highly in the testis and moderately in the prostate, marrow and peripheral blood cells. However, the function of human CMTM2 remains unknown. Here, we found that CMTM2 was upregulated in 5α-dihydrotestos-terone （DHT）-treated LNCaP cells. We investigated the relationship between CMTM2 and the androgen receptor. Our results showed that CMTM2 enhanced DHT-mediated androgen receptor （AR） transactivation and the expression of prostate specific antigen （PSA）. We also observed that CMTM2 enhanced the AR protein level, which was reversed by silencing endogenous CMTM2 expression, which suggested that CMTM2 might play an important role in maintaining the AR protein level. We also found that CMTM2 suppressed Akt activation. A previous study showed that Akt could phosphorylate AR at Ser210 and Ser790 and lead to AR ubiquitylation and degradation as well as suppression of AR activity. Taken together, suppressing Akt activation and increasing the AR protein level might be one of the mechanisms for the CMTM2-mediated enhancement of AR transactivation.

关 键 词：雄激素受体 转录 人类 LNCAP细胞 诱导 配体 蛋白水平 外周血细胞 

分 类 号：Q579.11[生物学—生物化学] Q75