title: Nuclear localization of p38 MAPK in response to DNA damage.
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.
authors: Department of Medicine/Immunobiology Program, University of Vermont, Burlington, 05405, USA.
authors: C David
authors: CD
authors: Wood
authors: Tina M
authors: TM
authors: Thornton
authors: Guadalupe
authors: G
authors: Sabio
authors: Roger A
authors: RA
authors: Davis
authors: Mercedes
authors: M
authors: Rincon
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D002453:Cell Cycle; D002467:Cell Nucleus / Q000201:enzymology*; D002478:Cells, Cultured; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D010766:Phosphorylation; D011995:Recombination, Genetic; D014965:X-Rays; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D048051:p38 Mitogen-Activated Protein Kinases