Current Cancer Drug Targets

Ruiwen Zhang 
Texas Tech University Health Sciences Center
1300 Coulter Drive
Amarillo, TX 79106
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Gadd45 Proteins as Critical Signal Transducers Linking NF-κB to MAPK Cascades

Author(s): Z. Yang, L. Song, C. Huang.

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., Gadd45α, Gadd45β, and Gadd45γ) play essential roles in connecting an upstream sensor module, the transcription Nuclear Factor-κB (NF-κB), to a transcriptional regulating module, mitogen-activated protein kinase (MAPK). This NF-κBGadd45( 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-κB and MAPK, are summarized. In the second part, the mechanisms by which Gadd45 proteins are regulated by NF-κB, and how they affect MAPK activation, are reviewed.

Keywords: GADD45α, Gadd45β, Gadd45γ, NF-κB, JNK, P38, Cell survival and apoptosis

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Article Details

VOLUME: 9
ISSUE: 8
Year: 2009
Page: [915 - 930]
Pages: 16
DOI: 10.2174/156800909790192383
Price: $58