Gadd45b mediates Fas-induced apoptosis by enhancing the interaction between p38 and retinoblastoma tumor suppressor

Hee Jun Cho, Sun Mi Park, Eun Mi Hwang, Kyoung Eun Baek, In Kyu Kim, In Koo Nam, Min Ju Im, Seung Ho Park, Seran Bae, Jae-Yong Park, Jiyun Yoo

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27 Citations (Scopus)

Abstract

Gadd45b has been known as a positive mediator of apoptosis induced by certain cytokines and oncogenes. Here, we identified Gadd45b as an effector of Fas-induced apoptosis and found that p38-mediated Rb hyperphosphorylation is one of the mechanisms of Fas-induced apoptosis in murine hepatocyte AML12 cells. Gadd45b has been shown to activate p38 through its physical interaction with MTK1 and induce apoptosis. However, in this study, we have showed that the function of Gadd45b during Fas-induced apoptosis in AML12 cells is different from that reported in previous studies. Depletion of Gadd45b expression did not inhibit the phosphorylation of p38, but it suppressed p38-mediated Rb phosphorylation and apoptosis in response to Fas stimulation by reducing the interaction between p38 and Rb. Ectopic expression of Gadd45b was sufficient to enhance this interaction. These findings suggest that Gadd45b mediates p38-induced Rb phosphorylation by enhancing the interaction between p38 and Rb during Fas-induced apoptosis in murine hepatocytes.

Original languageEnglish
Pages (from-to)25500-25505
Number of pages6
JournalJournal of Biological Chemistry
Volume285
Issue number33
DOIs
Publication statusPublished - 2010 Aug 13
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Cho, H. J., Park, S. M., Hwang, E. M., Baek, K. E., Kim, I. K., Nam, I. K., Im, M. J., Park, S. H., Bae, S., Park, J-Y., & Yoo, J. (2010). Gadd45b mediates Fas-induced apoptosis by enhancing the interaction between p38 and retinoblastoma tumor suppressor. Journal of Biological Chemistry, 285(33), 25500-25505. https://doi.org/10.1074/jbc.M109.091413