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Description

Growth arrest and DNA damage-inducible protein GADD45 alpha (UniProt P24522, also known as DDIT-1, DNA damage-inducible transcript 1 protein) is encoded by the GADD45A (also known as DDIT1, GADD45) gene (Gene ID 1647) in human. GADD45A, GADD45B, and GADD45G constitute a family of sensors that can mediate rapid responses to a variety of stressors in mammals. GADD45 proteins are involved in cellular DNA repair, cell cycle, cell survival, apoptosis, senescence, and DNA demethylation under various stress conditions. The interaction of GADD45 with PCNA regulates DNA replication and repair by stimulating nucleotide excision repair. GADD45 can induce cell cycle arrest through direct interaction with cell cycle-related protein CDK1 and p21. Direct phosphorylation of MEKK4 by GADD45 leads to activation of JNK and p38 kinase, resulting in cellular apoptosis and senescence, respectively. All GADD45 proteins are able to interact with each other and form homo- or hetero-dimers, which are crucial for GADD45 functions. GADD45 proteins are ubiquitously expressed, but can vary in their tissue expression patterns among the three members. Gadd45a deletion in mice causes genomic instability, resulting in defective mitosis and cytokinesis, as wll as increased radiation carcinogenesis. In addition to the reported antitumor activity via the induction of cellular apoptosis or senescence in cancer cells, GADD45A has also been shown to play a role in facilitating tumorigenesis in certain cancers.