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DCUN1D3 activates SCFSKP2 ubiquitin E3 ligase activity and cell cycle progression under UV damage

Shuai Zhang1, Jing Huang1, Taiping Shi1,2

  • 1Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, China.

Oncotarget
|August 20, 2016
PubMed

Insights

Loss of DCUN1D3 (also called SCCRO3) impairs DNA repair by preventing p27 protein degradation, leading to S phase arrest after UV damage. This study reveals DCUN1D3

Area of Science:

  • Cell Cycle Regulation
  • DNA Damage Response
  • Ubiquitin-Proteasome System

Background:

  • Previous studies indicated DCUN1D3 (also known as SCCRO3 or DCNL3) knockdown blocks S phase progression post-UV irradiation.
  • DCUN1D3 is implicated in cellular responses to DNA damage.

Purpose of the Study:

  • To elucidate the mechanism by which DCUN1D3 influences S phase progression after UV irradiation.
  • To investigate the interaction of DCUN1D3 with CAND1 and its role in the SCFSKP2 complex.

Main Methods:

  • DCUN1D3 knockdown and overexpression.
  • Co-immunoprecipitation assays.
  • Western blotting to assess protein levels and neddylation.

Main Results:

  • DCUN1D3 knockdown increases p27 protein levels post-UV irradiation.
  • DCUN1D3 interacts with CAND1, and their combined manipulation causes S phase arrest.
  • DCUN1D3 deficiency reduces Cullin-1 neddylation, inhibiting SCFSKP2 complex formation.
  • Accumulation of p27 in DCUN1D3-deficient cells leads to S phase block.

Conclusions:

  • DCUN1D3 is crucial for regulating S phase progression following UV damage.
  • DCUN1D3 facilitates SCFSKP2-mediated p27 degradation by promoting Cullin-1 neddylation.
  • The absence of DCUN1D3 results in p27 accumulation and subsequent S phase arrest.
Keywords:
CAND1DCUN1D3SCFSKP2cell cyclep27

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