asb9 interacts with ubiquitous mitochondrial creatine kinase and inhibits mitochondrial functionasb9与无处不在的线粒体肌酸激酶相互作用和抑制线粒体功能.pdfVIP

Kwon et al. BMC Biology 2010, 8:23 /1741-7007/8/23 RESEARCH ARTICLE Open Access ASB9 interacts with ubiquitous mitochondrial creatine kinase and inhibits mitochondrial function 1 1 2 3 4 4 3* Sanghoon Kwon , Dongbum Kim , Jae Won Rhee , Jeong-A Park , Dae-Won Kim , Doo-Sik Kim , Younghee Lee , Hyung-Joo Kwon1,2* Abstract Background: The ankyrin repeat and suppressor of cytokine signalling (SOCS) box proteins (Asbs) are a large protein family implicated in diverse biological processes including regulation of proliferation and differentiation. The SOCS box of Asb proteins is important in a ubiquitination-mediated proteolysis pathway. Here, we aimed to evaluate expression and function of human Asb-9 (ASB9). Results: We found that a variant of ASB9 that lacks the SOCS box (ASB9ΔSOCS) was naturally detected in human cell lines but not in peripheral blood mononuclear cells or normal hepatocytes. We also identified ubiquitous mitochondrial creatine kinase (uMtCK) as a new target of ASB9 in human embryonic kidney 293 (HEK293) cells. The ankyrin repeat domains of ASB9 can associate with the substrate binding site of uMtCK in a SOCS box- independent manner. The overexpression of ASB9, but not ASB9ΔSOCS, induces ubiquitination of uMtCK. ASB9 and ASB9ΔSOCS can interact and colocalise with uMtCK in the mitochondria. However, only expression of ASB9 induced abnormal mitochondrial structure and a decrease of mitochondrial membrane potential. Furthermore, the creatine kinase activities and cell growth were significantly reduced by ASB9 but not by ASB9ΔSOCS. Conclusions: ASB9 interacts with the creatine kinase system and negatively regulates cell growth. The differential ex