title: Cbl regulates the activity of SIRT2.
abstract: SIRT2 is a member of the sirtuin family of NAD(+)-dependent protein deacetylases. It is involved in metabolic homeostasis and has been linked to the progression of age-related diseases. Casitas B-lineage lymphoma (Cbl) proteins regulate signal transduction through many pathways and, consequently, regulate cell function and development. Cbl proteins are ubiquitin ligases that ubiquitinate and target many signaling molecules for degradation. The function of SIRT2 is modulated by post-translational modifications. However, the precise molecular signaling mechanism of SIRT2 through interactions with Cbl proteins has not yet been established. In this study, we investigated the potential regulation of SIRT2 function by the Cbl mammalian family members Cbl-b and c-Cbl. We found that Cbl-b and c-Cbl increased the protein level and stability of SIRT2 and that Cbl-b and c-Cbl interact with SIRT2. They were also found to regulate the deacetylase activity of SIRT2. Further investigation revealed that Cbl-mediated SIRT2 regulation occurred via ubiquitination of SIRT2.
authors.affiliation: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju, South Korea.
authors.forename: You Hee
authors.initials: YH
authors.lastname: Choi
authors.affiliation: College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon, South Korea.
authors.forename: Hangun
authors.initials: H
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju, South Korea.
authors.forename: Younho
authors.initials: Y
authors.lastname: Han
authors.affiliation: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju, South Korea.
authors.forename: Yun-Hye
authors.initials: YH
authors.lastname: Jin
authors.affiliation: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju, South Korea. Electronic address: kwanglee@chonnam.ac.kr.
authors.forename: Kwang Youl
authors.initials: KY
authors.lastname: Lee
mesh_terms: D002460:Cell Line; D006801:Humans; D011499:Protein Processing, Post-Translational; D050721:Proto-Oncogene Proteins c-cbl / Q000502:physiology*; D056565:Sirtuin 2 / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D016159:Tumor Suppressor Protein p53; D050721:Proto-Oncogene Proteins c-cbl; C474199:SIRT2 protein, human; D056565:Sirtuin 2; C067419:CBL protein, human
keywords: Cbl; Protein stability; SIRT2; Ubiquitination