Gadd45 Stress Sensor Genes

By: Dan A. Liebermann and Barbara Hoffman

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Synopsis: Emerging evidence indicates that the Gadd45 family of genes play a unique and critical role as sensors of stress, including genotoxic, physiological and oncogenic stress. The stress response Gadd45 family of genes (Gadd45a, Gadd45b & Gadd45g), discovered by Dr. Liebermann and other researchers, encode for small (18 kd) nuclear/cytoplasmic proteins). These genes are rapidly induced by a wide variety of endogenous and exogenous stress stimuli. In spite of marked similarities, Gadd45 genes are regulated differently & exhibit functional diversity. Gadd45 are implicated in cell cycle arrest, DNA demethylation & repair, apoptosis, cell survival, genomic stability, inflammation, & in response to physiological and oncogenic stress. Functions of Gadd45 genes are mediated by protein-protein interactions that modulate structure/function of other cellular proteins implicated in cell cycle regulation and the response of cells to stress; these interactions vary depending upon the biological setting including cell type, developmental stage and stress/stimulus. Protein partners include cdc2/cyclinB1, p21, the p38/JNK stress induced kinase pathways, and PCNA/histones. The purpose of this book is to provide a comprehensive picture of the unique global role Gadd45 genes play as stress sensors & the molecular pathways involved.