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Int J Biol Sci 2009; 5(5):428-437. doi:10.7150/ijbs.5.428 This issue Cite

Research Paper

Nuclear Localization of p38 MAPK in Response to DNA Damage

C. David Wood¹, Tina M. Thornton¹, Guadalupe Sabio², Roger A. Davis², Mercedes Rincon^{1 ✉}

1. Department of Medicine/Immunobiology Program, University of Vermont, Burlington, VT 05405. USA.
2. Program in Molecular Medicine, University of Massachusetts, Worcester, MA 01605. USA.

✉ Correspondence to: Mercedes Rincon, tel: +1 802 656 0937; fax: +1 802 656 3854; email: mercedes.rinconedu

Abstract

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.

Keywords: p38 MAP kinase, DNA damage, cell cycle checkpoint, DNA repair

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