GADD45B

Official Full Name

growth arrest and DNA damage inducible beta

Organism

Homo sapiens

Gene ID

4616

Background

This gene is a member of a group of genes whose transcript levels are increased following stressful growth arrest conditions and treatment with DNA-damaging agents. The genes in this group respond to environmental stresses by mediating activation of the p38/JNK pathway. This activation is mediated via their proteins binding and activating MTK1/MEKK4 kinase, which is an upstream activator of both p38 and JNK MAPKs. The function of these genes or their protein products is involved in the regulation of growth and apoptosis. These genes are regulated by different mechanisms, but they are often coordinately expressed and can function cooperatively in inhibiting cell growth. [provided by RefSeq, Jul 2008]

Synonyms

MYD118; GADD45BETA

Cat.No.	Product Name	Price
CSC-DC006036	Panoply™ Human GADD45B Knockdown Stable Cell Line	Inquiry
CSC-SC006036	Panoply™ Human GADD45B Over-expressing Stable Cell Line	Inquiry
CSC-RT0899	Human GADD45B Knockout Cell Line-HeLa	Inquiry
CLKO-0391	GADD45B KO Cell Lysate-HeLa	Inquiry

Cat.No.	Product Name	Price
AD06542Z	Human GADD45B adenoviral particles	Inquiry
LV13298L	human GADD45B (NM_015675) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHH075017	shRNA set against Mouse Gadd45b(NM_008655.1)	Inquiry
SHH075053	shRNA set against Rat Gadd45b(NM_001008321.1)	Inquiry
SHH298701	shRNA set against Human GADD45B (NM_015675.3)	Inquiry
SHH298705	shRNA set against Mouse GADD45B (NM_008655.1)	Inquiry
SHH298709	shRNA set against Rat GADD45B (NM_001008321.1)	Inquiry
SHW002400	shRNA set against Chicken GADD45B (NM_001044666)	Inquiry
SHW018155	shRNA set against Danio rerio GADD45BA (NM_213031)	Inquiry

Cat.No.	Product Name	Price
CDCB179630	Danio rerio GADD45BA ORF Clone (NM_213031)	Inquiry
CDCS414035	Human GADD45B ORF Clone (BC113466)	Inquiry
CDFR001783	Rat Gadd45b cDNA Clone(NM_001008321.1)	Inquiry
MiUTR1M-04899	GADD45B miRNA 3'UTR clone	Inquiry
MiUTR1R-02024	GADD45B miRNA 3'UTR clone	Inquiry
MiUTR3H-07237	GADD45B miRNA 3'UTR clone	Inquiry
SKO0277	GADD45B Validated sgRNA vector	Inquiry
CDCB157717	Human GADD45B ORF clone (BC113466)	Inquiry
CDCB163875	Chicken GADD45B ORF Clone (NM_001044666)	Inquiry
CDCL110329	Human Gadd45b ORF clone (NM_008655.1)	Inquiry
CDCR368850	Rat Gadd45b ORF Clone(NM_001008321.1)	Inquiry

Detailed Information

GADD45B is a member of the growth arrest DNA damage-inducible gene (GADD45) family, which consists of GADD45A (GADD45), GADD45B (MYD118), and GADD45G (cytokine response gene 6). This gene family encodes small, evolutionarily conserved proteins, sharing homology and high acidity. GADD45B was previously identified as a primary response gene in myeloid differentiation activated by interleukin-6 in the mouse myeloid leukemia cell line M1, which is associated with cell apoptosis, cell growth control, and cellular responses to DNA damage. Several studies on non-neuronal cells have indicated Gadd45b as an anti-apoptosis gene. Gadd45b was identified as an intrinsic neuroprotective molecule in retinal ganglion cells.

Gadd45b and neuronal apoptosis

Gadd45 has been identified as a stress-response gene to physiological or environmental conditions, and is originally induced by genotoxic agents. Gadd45a has been demonstrated as a pro-apoptosis gene in neuronal injuries and Gadd45b has been implicated as an anti-apoptosis factor. The recent research showed that Gadd45b inhibits neuronal apoptosis after cerebral ischemia. Gadd45b is significantly involved in preventing RGC death, which is consistent with its anti-apoptotic role in neurons. Gadd45b also inhibits apoptosis in other cell types, such as INS-1Eb and NIH3T3 cells. By contrast, Gadd45b was found to induce apoptotic death in cardiomyocytes, murine hepatocytes, and other cell types. Therefore, the function of Gadd45b in apoptosis appears to be cell type specific.

Gadd45b reduces brain apoptosis, but the mechanism of Gadd45b in apoptosis is not clear. Gadd45b could regulate apoptosis through regulating BDNF and downstream regulatory apoptotic proteins in ischemic stroke. First, Gadd45b promote regulates DNA demethylation of the regulatory regions of BDNF. Gadd45b knockout mice show a decrease in the BDNF gene expression. Second, a number of previous studies have clearly shown that activating BDNF-associated apoptotic proteins inhibits neuronal apoptotic cell death. Thirdly, the study indicated that Gadd45b-RNAi treatment obviously down-regulated BDNF expression and subsequent apoptosis after ischemic brain injury.

GADD45B and cancer

Colorectal carcinoma (CRC) carcinogenesis is a complicated and multifactorial process resulting from a number of environmental exposures. This process involves the combined actions of multiple oncogenes and tumor suppressor genes. As a negative growth-control gene, GADD45B is implicated in DNA damage, cell cycle arrest, and apoptosis. Higher expressions of GADD45B are associated with a higher risk of recurrence based on a cluster analysis of patients with stage II/III colon cancer treated with surgery alone or surgery plus adjuvant fluorouracil plus leucovorin. A recent study suggested that GADD45B was significantly up-regulated in CRC. Accordingly, it can postulate that abnormal expression of GADD45B could be involved with the carcinogenesis of CRC and it showed potential for use as a prognostic marker in future.

Several studies have reported that GADD45B was decreased in human hepatocellular carcinoma (HCC). Compared with the high levels of staining in colon cancer, prostate cancer, breast cancer, lymphoma, squamous cell carcinoma, and leiomyosarcoma, the under-expression of GADD45B was specific to liver cancer. As a novel pituitary tumor suppressor, microarray data showed the loss of GADD45B in gonadotrope tumors where its repression modulates cell proliferation, survival, and tumorigenicity. The hierarchical clustering of 19 pancreatic neuroendocrine tumors (PNETs) revealed that GADD45B was one of the most highly upregulated genes in the malignant group of PNETs. Thus, there is still controversy regarding the expression and function of GADD45B in multiple tumors. Abnormal expression of GADD45B is similar to tumor suppressor p53 and phosphatase and tensin homologue (PTEN), both of which showing high expression in some head and neck cancers, and mammary cancer. Further investigations are needed to determine the underlying mechanisms behind the dysfunction of GADD45B and CRC tumorigenesis.

References:

Wang L, et al. Abnormal expression of GADD45B in human colorectal carcinoma. Journal of Translational Medicine, 2012, 10(1):215-215.
Magimaidas A, et al. Gadd45b deficiency promotes premature senescence and skin aging. Oncotarget, 2016, 7(19):26935-26948.
Liu B, et al. Gadd45b is a Novel Mediator of Neuronal Apoptosis in Ischemic Stroke. International Journal of Biological Sciences, 2015, 11(3):353-60.
Liu B, et al. TGFβ signaling induces expression of Gadd45b in retinal ganglion cells. Investigative Ophthalmology & Visual Science, 2013, 54(2):1061-1069.

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