SIRT1 suppresses cellular accumulation of β-TrCP E3 ligase via protein degradation

•SIRT1 serves as an upstream negative regulator of β-TrCP.•SIRT1 depletion induces β-TrCP accumulation.•SIRT1 suppresses β-TrCP accumulation induced by resveratrol.•SIRT1 participates in promoting β-TrCP degradation.•SIRT1 suppression of β-TrCP synthesis occurs via post-translational degradation of...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2013-11, Vol.441 (4), p.831-837
Main Authors: Woo, Seon Rang, Byun, Jae Gwang, Kim, Yang Hyun, Park, Eun-Ran, Joo, Hyun-Yoo, Yun, Miyong, Shin, Hyun-Jin, Kim, Su-Hyeon, Shen, Yan Nan, Park, Jeong-Eun, Park, Gil-Hong, Lee, Kee-Ho
Format: Article
Language:English
Subjects:
beta-Transducin Repeat-Containing Proteins - metabolism
Glucose - deficiency
HCT116 Cells
HEK293 Cells
HeLa Cells
Humans
Nucleus
Post-translational degradation
Proteasome Endopeptidase Complex - metabolism
Proteasome Inhibitors - pharmacology
Protein Biosynthesis
Proteolysis
Pyruvate
Resveratrol
RNA, Messenger - metabolism
SIRT1
Sirtuin 1 - genetics
Sirtuin 1 - metabolism
Stilbenes - pharmacology
Transcription, Genetic
Ubiquitin-Protein Ligases - metabolism
β-TrCP
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Summary:•SIRT1 serves as an upstream negative regulator of β-TrCP.•SIRT1 depletion induces β-TrCP accumulation.•SIRT1 suppresses β-TrCP accumulation induced by resveratrol.•SIRT1 participates in promoting β-TrCP degradation.•SIRT1 suppression of β-TrCP synthesis occurs via post-translational degradation of the protein. 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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2013.10.146