PMID: 9553040May 30, 1998Paper

Cytokine rescue of p53-dependent apoptosis and cell cycle arrest is mediated by distinct Jak kinase signaling pathways

Genes & Development
F W QuelleG P Zambetti

Abstract

Exposure of hematopoietic progenitors to gamma-irradiation (IR) induces p53-dependent apoptosis and a p53-independent G2/M cell cycle arrest. These responses to DNA-damage can be inhibited by treatment with cytokine growth factors. Here we report that gamma-IR-induced apoptosis and cell cycle arrest are suppressed by specific cytokines (e.g., erythropoietin and interleukin-3) and that activation of the Jak kinase is necessary and sufficient for these effects. Using myleoid cells expressing a series of erythropoietin receptor (EpoR) mutants, we have demonstrated that Jak kinase-dependent signals initiated from the membrane proximal domain of EpoR were sufficient to prevent IR-induced apoptotic cell death, but failed to prevent cell cycle arrest. Cell survival by Epo did not require activation of other known signaling pathways including PI-3 kinase, PLC-gamma, Ras or Stats. Signaling targets of Jak kinase pathways included members of the Bcl-2 family of anti-apoptotic proteins, and enforced expression of Bcl-2 or Bcl-xL was as effective as cytokine treatment in blocking IR-induced apoptosis but did not prevent growth arrest. A distinct signal derived from a membrane distal domain of EpoR is required to overcome growth arrest asso...Continue Reading

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Citations

Mar 17, 2007·Apoptosis : an International Journal on Programmed Cell Death·Chun-Shiang ChungAlfred Ayala
Oct 6, 2007·Immunologic Research·Frederick W Quelle
Mar 31, 2000·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·K J O'ByrneA L Harris
Oct 22, 2011·Cell Death and Differentiation·S P GarrisonG P Zambetti
Dec 14, 1999·Molecular and Cellular Biology·Z GuG P Zambetti
Jan 3, 2001·Molecular and Cellular Biology·R WenJ L Cleveland
Oct 4, 2005·Molecular and Cellular Biology·Emanuela ColomboPier Giuseppe Pelicci
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Jan 21, 2011·BMC Cancer·Joëlle RubertThomas Radimerski
Jul 11, 2006·International Journal of Environmental Research and Public Health·Waneene C DorseyByron D Ford
Dec 23, 1998·Proceedings of the National Academy of Sciences of the United States of America·T NakaT Kishimoto
Feb 3, 2016·The Journal of Experimental Medicine·Jeffrey J BednarskiBarry P Sleckman
Apr 7, 2009·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Lan DingQiong Zhang
Mar 23, 2005·Critical Reviews in Oncology/hematology·Veerendra Munugalavadla, Reuben Kapur
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Dec 23, 2016·Cell Death & Disease·Zhuo RenJacques De Grève
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Apr 30, 2003·Cell Death and Differentiation·J D Weber, G P Zambetti
Jan 24, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Rachel Zhande, Aly Karsan

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