ASB9 interacts with ubiquitous mitochondrial creatine kinase and inhibits mitochondrial function

BMC Biology

Research Article

Jae Won Rhee¹  Jeong-A Park²  Younghee Lee²  Dae-Won Kim³  Doo-Sik Kim³  Dongbum Kim⁴  Sanghoon Kwon⁴  Hyung-Joo Kwon⁵ 

[1] Center for Medical Science Research, College of Medicine, Hallym University, Gangwon-do, Republic of Korea;Department of Biochemistry, College of Natural Sciences, Chungbuk National University, Chungbuk, Republic of Korea;Department of Biochemistry, College of Science, Yonsei University, Seoul, Republic of Korea;Department of Microbiology, College of Medicine, Hallym University, Gangwon-do, Republic of Korea;Department of Microbiology, College of Medicine, Hallym University, Gangwon-do, Republic of Korea;Center for Medical Science Research, College of Medicine, Hallym University, Gangwon-do, Republic of Korea;

关键词: Reverse Transcription Polymerase Chain Reaction;    HEK293 Cell;    Human Cell Line;    Adenylate Kinase;    Substrate Binding Site;   

DOI  :  10.1186/1741-7007-8-23

 received in 2009-12-24, accepted in 2010-03-19,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundThe 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).ResultsWe 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.ConclusionsASB9 interacts with the creatine kinase system and negatively regulates cell growth. The differential expression and function of ASB9 and ASB9ΔSOCS may be a key factor in the growth of human cell lines and primary cells.

【 授权许可】

CC BY   
© Kwon et al; licensee BioMed Central Ltd. 2010