A novel Chk1/2-Lats2-14-3-3 signaling pathway regulates P-body formation in response to UV damage

Nobuhiro Okada, Norikazu Yabuta, Hirokazu Suzuki, Yael Aylon, Moshe Oren, Hiroshi Nojima

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Proper response to DNA damage is essential for maintaining the integrity of the genome. Here we show that in response to ultraviolet (UV) radiation, the Lats2 tumor suppressor protein is phosphorylated predominantly by Chk1 and weakly by Chk2 at S408 in vivo, and that this process occurs at all stages of the cell cycle and leads to phosphorylation of 14-3-3γ on S59 by Lats2. Interaction of Lats2 and 14-3-3γ in vivo was confirmed by immunoprecipitation and western blot analysis. Phosphorylated 14-3-3γ translocates to the P-body, where mRNA degradation, translational repression and mRNA surveillance take place. Depletion of Lats2 or 14-3-3γ by siRNA inhibits P-body formation in response to UV, newly implicating Lats2 and 14-3-3 as regulators of P-body formation. By contrast, siRNA-mediated depletion of Lats1, a mammalian paralog of Lats2, showed no such effect. On the basis of these findings, we propose that the Chk1/2-Lats2-14-3-3 axis identified here plays an important role in connecting DNA damage signals to P-body assembly.

Original languageEnglish
Pages (from-to)57-67
Number of pages11
JournalJournal of cell science
Volume124
Issue number1
DOIs
Publication statusPublished - Jan 1 2011

Keywords

  • 14-3-3
  • Chk1
  • DNA damage
  • Lats/Warts
  • P-body

ASJC Scopus subject areas

  • Cell Biology

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