title: SIRT1 suppresses cellular accumulation of β-TrCP E3 ligase via protein degradation.
abstract: β-Transducin repeat-containing protein (β-TrCP), an E3 ligase, promotes the degradation of substrate proteins in response to various stimuli. Even though several β-TrCP substrates have been identified to date, limited information of its upstream regulators is available. Here, we showed that SIRT1 suppresses β-TrCP protein synthesis via post-translational degradation. SIRT1 depletion led to a significant increase in the β-TrCP accumulation without affecting the mRNA level. Consistently, β-TrCP protein accumulation induced by resveratrol was further enhanced upon SIRT1 depletion. Rescue of SIRT1 reversed the effect of resveratrol, leading to reduced β-TrCP protein levels. Proteasomal inhibition led to recovery of β-TrCP in cells with SIRT1 overexpression. Notably, the recovered β-TrCP colocalized mostly with SIRT1. Thus, SIRT1 acts as a negative regulator of β-TrCP synthesis via promoting protein degradation.
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea.
authors.forename: Seon Rang
authors.initials: SR
authors.lastname: Woo
authors.forename: Jae Gwang
authors.initials: JG
authors.lastname: Byun
authors.forename: Yang Hyun
authors.initials: YH
authors.lastname: Kim
authors.forename: Eun-Ran
authors.initials: ER
authors.lastname: Park
authors.forename: Hyun-Yoo
authors.initials: HY
authors.lastname: Joo
authors.forename: Miyong
authors.initials: M
authors.lastname: Yun
authors.forename: Hyun-Jin
authors.initials: HJ
authors.lastname: Shin
authors.forename: Su-Hyeon
authors.initials: SH
authors.lastname: Kim
authors.forename: Yan Nan
authors.initials: YN
authors.lastname: Shen
authors.forename: Jeong-Eun
authors.initials: JE
authors.lastname: Park
authors.forename: Gil-Hong
authors.initials: GH
authors.lastname: Park
authors.forename: Kee-Ho
authors.initials: KH
authors.lastname: Lee
mesh_terms: D005947:Glucose / Q000172:deficiency; D045325:HCT116 Cells; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000494:pharmacology; D014176:Protein Biosynthesis; D059748:Proteolysis; D012333:RNA, Messenger / Q000378:metabolism; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology; D014158:Transcription, Genetic; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D044844:beta-Transducin Repeat-Containing Proteins / Q000378:metabolism*
chemical_list: C471644:BTRC protein, human; D061988:Proteasome Inhibitors; D012333:RNA, Messenger; D013267:Stilbenes; D044844:beta-Transducin Repeat-Containing Proteins; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D005947:Glucose; D000077185:Resveratrol
keywords: Nucleus; Post-translational degradation; Pyruvate; Resveratrol; SIRT1; β-TrCP