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Function
Gadd45g has several different functions in humans, including sexual development, human-specific brain development, tumor suppression, and the cellular stress response. In general, Gadd45g interacts with several other proteins that are involved in DNA repair, cell cycle control, apoptosis, and senescence.

In the male sexual development pathway, Gadd45g is essential for activating SRY, leading to proper formation of the gonads and sex-determination. Deletion of an enhancer close to the Gadd45g gene is correlated to increased proliferation of neuronal cells, which could account for part of the difference in neural development between humans and other species. After DNA damage, Gadd45g helps to prevent tumor formation by its apoptosis-inducing interactions with the MTK/MEKK4 kinases, which are upstream of p38/JNK. Gadd45g is in turn regulated upstream by NF-κB. It it also involved in repression of the cell cycle through the G2/M checkpoint.

Interactions
GADD45G is involved with dental epithelial cell proliferation. GADD45g regulates cell proliferation and gene expression where it is an active gene. GADD45G is expressed in enamel knots. The gene regulates p21-mediated epithelial cell proliferation by activating the p38 MAPK pathway during the development of teeth.

Clinical Significance
Generally, in numerous kinds of cancerous cells, GADD45G is down regulated. There is a low expression due to methylation of the GADD45G promotor.

GADD45G is related to esophageal cancer. GADD45G is silenced by methylation in these cancer cells. The expression level and methylation status are involved in the prognosis of esophageal squamous cell carcinoma. Demethylation of the gene may have a therapeutic advantage in esophageal cancer.

In hepatocellular carcinoma cells GADD45G is down regulated.It participates in negatively regulating the Jak-Stat3 signaling pathway. It acts as a tumor suppressor in HCC cells by inducing growth arrest or cellular senescence. When GADD45G expression is low, liver cells may be able to avoid the growth arrest stage of the cell life cycle.

Human Tissue Distribution
GADD45G is expressed most in the skeletal muscle, kidney and liver. This gene has a low expression in the heart, brain, spleen, lung and testis.

Discovery
GADD45G was originally cloned by Beadling under the name CR6 in 1993, and its function as a tumor suppressor was discovered in 1999 by Zhang.