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Review
. 2009 Dec;9(8):915-30.
doi: 10.2174/156800909790192383.

Gadd45 proteins as critical signal transducers linking NF-kappaB to MAPK cascades

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Review

Gadd45 proteins as critical signal transducers linking NF-kappaB to MAPK cascades

Z Yang et al. Curr Cancer Drug Targets. 2009 Dec.

Abstract

The growth arrest and DNA damage-inducible 45 (Gadd45) proteins are a group of critical signal transducers that are involved in regulations of many cellular functions. Accumulated data indicate that all three Gadd45 proteins (i.e., Gadd45alpha, Gadd45beta, and Gadd45gamma) play essential roles in connecting an upstream sensor module, the transcription Nuclear Factor-kappaB (NF-kappaB), to a transcriptional regulating module, mitogen-activated protein kinase (MAPK). This NF-kappaB-Gadd45(s)-MAPK pathway responds to various kinds of extracellular stimuli and regulates such cell activities as growth arrest, differentiation, cell survival, and apoptosis. Defects in this pathway can also be related to oncogenesis. In the first part of this review, the functions of Gadd45 proteins, and briefly NF-kappaB and MAPK, are summarized. In the second part, the mechanisms by which Gadd45 proteins are regulated by NF-kappaB, and how they affect MAPK activation, are reviewed.

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Figures

Fig 1
Fig 1
NF-κB regulates Gadd45 levels by various mechanisms. 1. Direct binding of promoter regions of Gadd45α/β. 2. Regulation of Gadd45(s)-associated transcription factors. 3. Increase of the stability of Gadd45α mRNA. 4. p50-mediated deubiquitination of Gadd45α protein.

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