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In Vivo Detection and Analysis of Rb Protein SUMOylation in Human Cells
09:40

In Vivo Detection and Analysis of Rb Protein SUMOylation in Human Cells

Published on: November 2, 2017

SUMO-modified nuclear cyclin D1 bypasses Ras-induced senescence

X D Wang1, E Lapi, A Sullivan

  • 1Nuffield Department of Clinical Medicine, Ludwig Institute for Cancer Research, University of Oxford, Oxford, UK.

Cell Death and Differentiation
|August 28, 2010
PubMed

Insights

Apoptosis-stimulating protein of p53 (ASPP) 2 suppresses Ras-induced senescence via a novel pathway. This study reveals SUMO modification as a key regulator of nuclear cyclin D1, impacting cell cycle entry and senescence.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Biology

Background:

  • Oncogene-induced senescence is a critical tumor suppressive mechanism.
  • The tumor suppressor apoptosis-stimulating protein of p53 (ASPP) 2 is a recently identified protein involved in cellular processes.

Purpose of the Study:

  • To investigate the role of ASPP2 in Ras oncogene-induced senescence.
  • To elucidate the novel p53/p19(Arf)/p21(waf1/cip1)-independent pathway mediated by ASPP2.
  • To identify new regulators of cell cycle entry and senescence.

Main Methods:

  • Investigated Ras oncogene-induced senescence.
  • Analyzed the role of ASPP2 in regulating nuclear cyclin D1 and retinoblastoma protein (Rb) phosphorylation.
  • Examined the effect of SUMO modification on cyclin D1.
  • Compared the potency of nuclear cyclin D1 versus wild-type (WT) cyclin D1 in bypassing senescence.

Main Results:

  • ASPP2 mediates Ras oncogene-induced senescence through a novel pathway independent of p53/p19(Arf)/p21(waf1/cip1).
  • ASPP2 suppresses small ubiquitin-like modifier (SUMO)-modified nuclear cyclin D1 and inhibits Rb phosphorylation.
  • Lysine residue K33 of cyclin D1 is crucial for this regulation.
  • Nuclear cyclin D1 is more potent than WT cyclin D1 in bypassing Ras-induced senescence.

Conclusions:

  • SUMO modification positively regulates nuclear cyclin D1.
  • ASPP2 acts as a tumor suppressor by inhibiting nuclear cyclin D1 and Rb phosphorylation.
  • A new mechanism regulating cell cycle entry and senescence involving SUMO modification of cyclin D1 is identified.

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