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

作者：Okada Nobuhiro; Yabuta Norikazu; Suzuki Hirokazu; Aylon Yael; Oren Moshe; Nojima Hiroshi^*

来源：Journal of Cell Science, 2011, 124(1): 57-67.

DOI：10.1242/jcs.072918

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

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 14-3-3 gamma on S59 by Lats2. Interaction of Lats2 and 14-3-3 gamma in vivo was confirmed by immunoprecipitation and western blot analysis. Phosphorylated 14-3-3 gamma translocates to the P-body, where mRNA degradation, translational repression and mRNA surveillance take place. Depletion of Lats2 or 14-3-3 gamma 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.

• 出版日期2011-1