Disease relevance of GADD45B

• In further studies of multiple human cancer tissues, GADD45beta strongly stained tissues such as colon cancer, breast cancer, prostate cancer, squamous cell cancer, lymphoma, and leiomyosarcoma, suggesting that the decreased expression of GADD45beta is specific to HCC [1].
• The results suggested that expression of GADD45beta was decreased in human liver cancer cell lines HepG2 and Hep3B, but not in normal human embryonic liver cell line CL-48 or normal liver tissue [1].
• Finally, comparison of control and AMG-treated melanoma cells by pathway-specific gene array analysis indicated that inhibition of NO synthesis led, before induction of apoptosis, to up-regulation of mRNA levels of genes involved in the apoptosis pathway such as Bax, caspase-1, caspase-3, caspase-6, gadd45beta, mdm2, and TRAIL [2].

High impact information on GADD45B

• Mechanistic studies showed that sulfasalazine selectively blocks nuclear factor-kappaB-dependent gene transcription, inhibits hepatic stellate cell expression of Gadd45beta, stimulates phosphorylation of Jun N-terminal kinase 2, and promotes apoptosis by a mechanism that is prevented by the Jun N-terminal kinase inhibitor SP600125 [3].
• The stress-inducible molecules GADD45beta and GADD45gamma have been implicated in regulating IFNgamma production in CD4 T cells [4].
• The U(L)41 protein thus mediates two functions, i.e., it mediates rapid degradation of some mRNAs exemplified by beta-actin and stabilizes or delays the degradation of other mRNAs exemplified by GADD45beta, tristetraprolin, etc [5].
• Here, we report that, in B cells, Gadd45 beta is induced by CD40 through a mechanism that requires NF-kappa B and that this induction suppresses Fas-mediated killing [6].
• These findings identify Gadd45 beta as a critical mediator of the prosurvival response to CD40 stimulation and provide important new insights into the apoptotic mechanism that is triggered by Fas in B cells [6].

Biological context of GADD45B

• However, in contrast to Bcl-xL, Gadd45 beta is unable to hamper the "intrinsic" pathway for apoptosis and in fact appears to block Fas cytotoxicity herein by suppressing a mitochondria-targeting mechanism activated by this receptor [6].
• GADD45beta is a primary cell cycle element responsive to NF-kappaB activation in anti-apoptotic responses [7].
• The present study provides evidence demonstrating that NK-kappaB, ERK and GADD45beta are co-activated by ionizing radiation (IR) in a pattern of mutually dependence to increase cell survival [7].
• A novel role for GADD45beta as a mediator of MMP-13 gene expression during chondrocyte terminal differentiation [8].
• Transfection of dominant negative mutant IkappaB that blocks NF-kappaB nuclear translocation, inhibited ERK activity and GADD45beta expression and increased cell radiosensitivity [7].

Anatomical context of GADD45B

• In the presence of Gadd45 beta, the Fas-induced apoptotic cascade is halted at mitochondria [6].
• These observations indicated that GADD45beta plays an essential role during chondrocyte terminal differentiation [8].
• Here we showed that in the SW620 human colon cancer cell line, TSA and butyrate induced the growth arrest and DNA damage gene 45alpha (GADD45alpha) and GADD45beta [9].

Regulatory relationships of GADD45B

• Moreover, the TFPI-induced expression of GADD45B was blocked by receptor-associated protein, which masks the ligand-binding domain of very low density lipoprotein receptor (VLDL-R) [10].

Other interactions of GADD45B

• Finally, stress response genes encoding GADD45B, ATF3, and TP53AP1 were upregulated [11].
• Tissue factor pathway inhibitor induces expression of JUNB and GADD45B mRNAs [10].
• Gadd45 beta mediates the protective effects of CD40 costimulation against Fas-induced apoptosis [6].
• Consistently, either GADD45beta or GADD45gamma bind to Cdc2 in vivo [12].
• A mutant with a deletion of the central region (residues 50-76), which is conserved in the family members GADD45beta and GADD45gamma, lacked such activity [12].

Analytical, diagnostic and therapeutic context of GADD45B

• By using DNA-array techniques and Northern blot analysis, we here revealed that TFPI transiently induced the mRNA expression of JUNB and GADD45B [10].
• Histochemistry study and real-time PCR further confirmed that GADD45beta staining in HCC was significantly decreased when compared to surrounding non-neoplastic liver tissue [1].

References