Program in Molecular Medicine
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Molecular Biology
p38 MAP kinase (MAPK) is activated in response to environmental stress, cytokines and DNA damage, and mediates death, cell differentiation and cell cycle checkpoints. The intracellular localization of p38 MAPK upon activation remains unclear, and may depend on the stimulus. We show here that activation of p38 MAPK by stimuli that induce DNA double strand breaks (DSBs), but not other stimuli, leads to its nuclear translocation. In addition, naturally occurring DSBs generated through V(D)J recombination in immature thymocytes also promote nuclear accumulation of p38 MAPK. Nuclear translocation of p38 MAPK does not require its catalytic activity, but is induced by a conformational change of p38 MAPK triggered by phosphorylation within the active site. The selective nuclear accumulation of p38 MAPK in response to DNA damage could be a mechanism to facilitate the phosphorylation of p38 MAPK nuclear targets for the induction of a G2/M cell cycle checkpoint and DNA repair.
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Citation: Int J Biol Sci. 2009 Jun 16;5(5):428-37. Available from http://www.ijbs.com/v05p0428.htm.
Copyright © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.
p38 MAP kinase, DNA damage, cell cycle checkpoint, DNA repair
Wood, C. David; Thornton, Tina; Sabio, Guadalupe; Davis, Roger J.; and Rincon, Mercedes, "Nuclear localization of p38 MAPK in response to DNA damage" (2009). Davis Lab Publications. 76.
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.