Apoptosis

, Volume 10, Issue 5, pp 1111–1120

p38 MAP kinase plays a role in G2 checkpoint activation and inhibits apoptosis of human B cell lymphoma cells treated with etoposide

  • T. Kurosu
  • Y. Takahashi
  • T. Fukuda
  • T. Koyama
  • T. Miki
  • O. Miura
Article

DOI: 10.1007/s10495-005-3372-z

Cite this article as:
Kurosu, T., Takahashi, Y., Fukuda, T. et al. Apoptosis (2005) 10: 1111. doi:10.1007/s10495-005-3372-z

Abstract

p38 MAPK is mainly activated by stress stimuli and mediates signals that regulate various cellular responses, including cell-cycle progression and apoptosis, depending on cell types and stimuli. Here we examine the role of p38 in regulation of apoptosis and cell cycle checkpoint in Daudi B-cell lymphoma cells treated with the topoisomerase II inhibitor etoposide. Etoposide activated p38, inhibited the G2/M transition with the persistent inhibitory phosphorylation of Cdc2 on Tyr15, and caused apoptosis of Daudi cells. Inducible expression of a dominant negative p38α mutant in Daudi cells reduced the inhibition of Cdc2 as well as G2/M arrest and augmented apoptosis induced by etoposide. SB203580, a specific inhibitor of p38α and p38β, similarly reduced the inhibitory phosphorylation of Cdc2 as well as G2/M arrest and augmented apoptosis of Daudi cells treated with etoposide. These results suggest that p38 plays a role in G2/M checkpoint activation through induction of the persistent inhibitory phosphorylation of Cdc2 and, thereby, inhibits apoptosis of Daudi cells treated with etoposide. The present study, thus, raises the possibility that p38 may represent a new target for sensitization of lymphoma cells to DNA-damaging chemotherapeutic agents.

Keywords

apoptosisetoposideG2 checkpointlymphomap38 MAP kinase

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • T. Kurosu
    • 1
  • Y. Takahashi
    • 1
  • T. Fukuda
    • 1
  • T. Koyama
    • 1
  • T. Miki
    • 1
  • O. Miura
    • 1
  1. 1.Department of HematologyTokyo Medical and Dental UniversityTokyoJapan