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Ubiquitinated sirtuin 1 (SIRT1) function is modulated during DNA damage-induced cell death and survival

Lirong Peng1, Zhigang Yuan1, Yixuan Li1

  • 1From the Department of Molecular Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida 33612.

The Journal of Biological Chemistry
|February 12, 2015
PubMed

Insights

Ubiquitination of Sirtuin 1 (SIRT1) is crucial for its function during DNA damage response (DDR). This post-translational modification regulates SIRT1

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Post-translational modifications like ubiquitination regulate cell signaling pathways.
  • Sirtuin 1 (SIRT1) is a key regulator of the DNA damage response (DDR).
  • The specific role of SIRT1 ubiquitination in DDR remains largely unknown.

Purpose of the Study:

  • To investigate the role and mechanisms of SIRT1 ubiquitination during DNA damage response.
  • To determine how SIRT1 ubiquitination impacts its localization, activity, and function in DDR.

Main Methods:

  • In vitro and in vivo ubiquitination assays.
  • Analysis of SIRT1 nuclear localization under varying ubiquitination states.
  • Assessment of SIRT1's role in cell death and survival pathways following DNA damage.

Main Results:

  • SIRT1 undergoes dynamic and distinct ubiquitination upon DNA damage.
  • MDM2 E3 ligase mediates SIRT1 ubiquitination.
  • Hypo-ubiquitination of SIRT1 impairs its nuclear localization.
  • SIRT1 ubiquitination influences its function in cell death and survival during DDR.

Conclusions:

  • Ubiquitination is a critical post-translational modification for SIRT1 function in DNA damage response.
  • SIRT1 ubiquitination by MDM2 is essential for proper nuclear localization and subsequent DDR signaling.
  • Understanding SIRT1 ubiquitination provides insights into cellular responses to DNA damage.
Keywords:
Deubiquitylation (Deubiquitination)Histone Deacetylase (HDAC)Post-translational Modification (PTM)SirtuinUbiquitylation (Ubiquitination)

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