Growth Arrest and DNA Damage-Inducible Protein GADD45 α (GADD45A) is a member of the GADD45 family. GADD45A can be induced by UV irradiation, X-rays, growth arrest and alkylating agents, of which can be mediated by some kinases other than PKC. GADD45A can interact with MAPK14, GADD45GIP1, PCNA. In T-cells, GADD45A functions as a regulator of p38 MAPKs by inhibiting p88 phosphorylation and activity. GADD45A may affect PCNA interaction with some cell division protein kinase complexes, stimulating DNA excision repair in vitro and inhibits entry of cells into S phase.

GADD45A is a member of the GADD45 Family, and has been found to associate with several cytoplasmic and nuclear factors and has been implicated in several cellular functions, including MAPK signaling, cell cycle regulation, DNA repair and genomic stability, apoptosis, and immune responses. The GADD45 Family of genes is rapidly induced by different stressors, including differentiation-inducing cytokines, and there is a large body of evidence that their cognate proteins are key players in cellular stress responses. GADD45A protein has been reported to interact with multiple important cellular proteins, including Cdc2 protein kinase, proliferating cell nuclear antigen (PCNA), p21Waf1/Cip1 protein, core histone protein and MTK/MEKK4, an up-stream activator of the JNK/SAPK pathway, indicating that GADD45A may play important roles in the control of cell cycle checkpoint, DNA repair process, and signaling transduction. GADD45A expression in response to genotoxic stress illustrates a more complex scenario, wherein transcriptional changes operate in concert with mRNA turnover and translational regulation. GADD45A was the first stress-inducible gene determined to be up-regulated by p53 and is also a target for the p53 homologues, p63 and p73. The decreased GADD45A expression is also considered a survival mechanism, as cancer cells without this control can evade the apoptotic pathway leading to increased tumourigenesis. As GADD45A is an essential component of many metabolic pathways that control proliferating cancer cells, it presents itself as an emerging drug target worthy of further investigation.

Growth Arrest and DNA Damage-Inducible Protein GADD45 Υ (GADD45G) is a nuclear protein which belongs to the GADD45 family. GADD45G is highly expressed in placenta. GADD45G interacts with various proteins whose transcript levels are increased following stressful growth arrest conditions and treatment with DNA-damaging agents. GADD45G responds to environmental stresses by mediating activation of the p38/JNK pathway via MTK1/MEKK4 kinase. GADD45G is also involved in the regulation of growth and apoptosis. GADD45G inhibits cell growth and differentiation by androgens. The mRNA expression is down-regulated in hepatocellular carcinoma.

GADD45G, also known as CR6, is part of the nuclear proteins to interact with various proteins whose transcript levels are raised after stressful growth arrest conditions and treatment with DNA-damaging agents. GADD45G reacts to environmental stresses by mediating activation of the p38/JNK pathway which is mediated through their protein binding and activating MTK1/MEKK4 kinase, which is an upstream activator of both p38 and JNK MAPKs. GADD45G acts as a new-age tumor suppressor however is being frequently inactivated epigenetically in multiple tumors. GADD45G mRNA expression is down-regulated in hepatocellular carcinoma. GADD45G causes cell cycle arrest at G2/M transition when transfected into Hep-G2 cells. GADD45G induction by androgens involves new protein synthesis. Overexpression of GADD45G inhibits cell growth and causes morphological modifications in prostate cell lines thus GADD45G takes part in differentiation induction by androgens.

Growth Arrest and DNA Damage-Inducible Protein GADD45 β (GADD45B) is a member of the GADD45 family. GADD45B has been shown to interact with MAP3K4, ASK1, MAP2K7, and GADD45GIP1. GADD45B is involved in the regulation of growth and apoptosis. GADD45B reacts to environmental stresses by mediating activation of stress-responsive MTK1/MEKK4 kinase, which is an upstream activator of both p38 and JNK MAPKs. In addition, GADD45B participates in the down-regulation of hepatocellular carcinoma (HCC). It may serve as a possible therapeutic target.