title: Serum starvation induces H2AX phosphorylation to regulate apoptosis via p38 MAPK pathway.
abstract: Phosphorylation of H2AX is believed to be associated with the repair of damaged DNA. Recent findings suggest a novel function of H2AX in cellular apoptosis. Specifically, it was shown that ultraviolet A-activated JNK phosphorylates H2AX to regulate apoptosis. Here we show that serum starvation induces H2AX phosphorylation and apoptosis independent of the JNK pathway. Serum starvation induced p38 phosphorylation, whereas it did not affect the phosphorylation of ERK or JNK. Inhibition of p38 reduced H2AX phosphorylation and apoptosis. Furthermore, p38 was found to phosphorylate H2AX directly in vitro and was colocalized with H2AX in vivo. Finally, we demonstrate that H2AX phosphorylation is required for serum starvation-induced apoptosis. Taken together, these data elucidate a novel signaling pathway (p38/H2AX) to regulate apoptosis.
authors.affiliation: The Aviation Medicine Research Lab, General Hospital of Air Force, Fucheng Road 30, Beijing 100036, China. luchengrong@263.net
authors.forename: Chengrong
authors.initials: C
authors.lastname: Lu
authors.forename: Ying
authors.initials: Y
authors.lastname: Shi
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Song
authors.forename: Meicai
authors.initials: M
authors.lastname: Zhu
authors.forename: Qing
authors.initials: Q
authors.lastname: Cai
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D044967:Serum; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D006657:Histones; D048051:p38 Mitogen-Activated Protein Kinases; C475961:gamma-H2AX protein, mouse