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 expression and function of ASB9 and ASB9ΔSOCS may be a key factor in the growth of human cell lines and primary cells.
|Publication status||Published - 2010 Mar 19|
Bibliographical noteFunding Information:
The authors are grateful to Seung-Hae Kwon at the Chuncheon Center of the Korea Basic Science Institute for technical assistance in confocal image analyses (LSM 510 META NLO). They are also grateful to Jin Han of Inje University for helpful discussion on the mitochondrial membrane potential analysis. This research was supported by a grant from Stem Cell Research Center of the 21st Century Frontier Research Program (SC-2260), a grant from the Next Generation Growth Engine Program (F104AC010002-06A0301-00230), and a grant from National Research Foundation (20090081761, 20090083296, 2009-0093812) funded by the Ministry of Education, Science and Technology, Republic of Korea.
All Science Journal Classification (ASJC) codes
- Structural Biology
- Ecology, Evolution, Behavior and Systematics
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)
- Plant Science
- Developmental Biology
- Cell Biology