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

Seon Rang Woo, Jae Gwang Byun, Yang Hyun Kim, Eun Ran Park, Hyun Yoo Joo, Miyong Yun, Hyun Jin Shin, Su Hyeon Kim, Yan Nan Shen, Jeong Eun Park, Gil-Hong Park, Kee Ho Lee

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7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)831-837
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume441
Issue number4
DOIs
Publication statusPublished - 2013 Nov 29

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Keywords

  • β-TrCP
  • Nucleus
  • Post-translational degradation
  • Pyruvate
  • Resveratrol
  • SIRT1

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Woo, S. R., Byun, J. G., Kim, Y. H., Park, E. R., Joo, H. Y., Yun, M., Shin, H. J., Kim, S. H., Shen, Y. N., Park, J. E., Park, G-H., & Lee, K. H. (2013). SIRT1 suppresses cellular accumulation of β-TrCP E3 ligase via protein degradation. Biochemical and Biophysical Research Communications, 441(4), 831-837. https://doi.org/10.1016/j.bbrc.2013.10.146