Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 281, Issue 26, Pages 17552-17558Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M600950200
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- NHLBI NIH HHS [R01 HL 70530-01] Funding Source: Medline
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Gadd45a, Gadd45b, and Gadd45g (Gadd45/MyD118/CR6) are genes that are rapidly induced by genotoxic stress and have been implicated in genotoxic stress-induced responses, notably in apoptosis. Recently, using myeloid-enriched bone marrow (BM) cells obtained from wild-type (WT), Gadd45a-deficient, and Gadd45b-deficient mice, we have shown that in hematopoietic cells Gadd45a and Gadd45b play a survival function to protect hematopoietic cells from DNA-damaging agents, including ultra violet (UV)-induced apoptosis. The present study was undertaken to decipher the molecular paths that mediate the survival functions of Gadd45a and Gadd45b against genotoxic stress induced by UV radiation. It is shown that in hematopoietic cells exposed to UV radiation Gaddd45a and Gadd45b cooperate to promote cell survival via two distinct signaling pathways involving activation of the GADD45a-p38-NF-kappa B-mediated survival pathway and GADD45b-mediated inhibition of the stress response MKK4-JNK pathway.
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