title: CHFR is negatively regulated by SUMOylation-mediated ubiquitylation.
abstract: CHFR ubiquitin ligase plays an important role in cell cycle progression and tumorigenesis. CHFR tumor suppressor function is highly associated with its protein level. We recently reported that CHFR protein levels are negatively regulated by SUMOylation-mediated proteasomal degradation. In the present study, we uncover a detailed molecular mechanism how SUMOylation promotes CHFR destabilization. We demonstrate that SUMO modification of CHFR promotes its ubiquitylation and subsequent proteasomal degradation. However, SUMOylation of CHFR does not affect its auto-ubiquitylation, which generally serves as a maintenance mechanism for most ubiquitin ligases. Moreover, the E3 ubiquitin ligase activity of CHFR is dispensable for this SUMOylation-mediated ubiquitylation and degradation. Conversely, SENP2 deSUMOylating enzyme reduces SUMOylation-induced ubiquitylation of CHFR, leading to elevated CHFR protein levels. Taken together, our results present a new regulatory mechanism for CHFR that sequential post-translational modifications of CHFR by SUMO and ubiquitin coordinately regulates its stability.
authors: School of Biological Sciences, Research Center for Functional Cellulomics, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Sung Jun
authors: SJ
authors: Bae
authors: Young Eun
authors: YE
authors: Kwon
authors: Myungjin
authors: M
authors: Kim
authors: Jae Hong
authors: JH
authors: Seol
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D000075223:Poly-ADP-Ribose Binding Proteins; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D025842:SUMO-1 Protein / Q000378:metabolism; D058207:Sumoylation; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D025842:SUMO-1 Protein; D025801:Ubiquitin; C412002:CHFR protein, human; D044767:Ubiquitin-Protein Ligases