GADD45A Research Reagents

Growth arrest and DNA damage-inducible protein GADD45 alpha is a protein in humans that is encoded by GADD45A gene. In T-cells, functions as a regulator of p38 MAPKs by inhibiting p88 phosphorylation and activity (By similarity). Might affect PCNA interaction with some CDK (cell division protein kinase) complexes; stimulates DNA excision repair in vitro and inhibits entry of cells into S phase.

The following GADD45A reagents supplied by CUSABIO are manufactured under a strict quality control system. Multiple applications have been validated and solid technical support is offered.

GADD45A Antibodies

GADD45A Antibodies for Homo sapiens (Human)

GADD45A Proteins

GADD45A Proteins for Homo sapiens (Human)

GADD45A Proteins for Rattus norvegicus (Rat)

GADD45A Proteins for Mus musculus (Mouse)

GADD45A Proteins for Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus)

GADD45A Proteins for Bos taurus (Bovine)

GADD45A Proteins for Felis catus (Cat) (Felis silvestris catus)

GADD45A ELISA Kit

GADD45A ELISA Kit for Homo sapiens (Human)

GADD45A Background

The GADD45A gene was initially isolated from Chinese Hamster Ovarian (CHO) cells based on rapid induction under UV exposure [1]. Growth arrest and DNA-damage-inducible protein 45 alpha (GADD45α/GADD45A) is one of the GADD45 family proteins that act as stress sensors that regulate the response of mammalian cells to genotoxic/physiological stress and modulate tumor formation. GADD45A is widely expressed and predominantly localized in nucluse [2]. Interacting with multiple important cellular proteins, GADD45A is responsive to numerous agents implicated in DNA damage, apoptosis, cell cycle checkpoint control, cell injury, and other growth regulatory processes [3]. GADD45A has roles both in S-phase and G2/M arrest [4][5]. It inhibits DNA replication during the S phase by replacing PCNA from the cyclin D1 complex [4]. Similarly, GADD45A binds to Cdk1, blocking its interaction with cyclin B1, thus suppressing Cdk1 activity, stagnating the cell at the G2/M checkpoint, and inducing apoptosis [6]. GADD45A appears to negatively modulate the tumor suppressor CDKN1A (cyclin-dependent kinase inhibitor 1 a) expression in keratinocytes, permitting nucleotide excision repair (NER) after UV radiation [3]. p38 phosphorylates p53, upregulating downstream effector GADD45A, which is contrarily conducive to activate p53 via p38 [5]. The process establishes a positive feedback loop that is transient during genotoxic stress-induced growth arrest, and that is required during oncogene-induced permanent growth arrest [7]. Therefore, mice deleted the GADD45A gene exhibited genomic instability, increased carcinogenesis, and a low frequency of exencephaly after genotoxic stresses such as ionizing radiation (IR) and UV radiation, consistently with previous study results [8]. These results also indicated that GADD45A is one component of the p53 pathway that contributes to the maintenance of genomic stability [8]. Besides, GADD45A also has a role in DNA-demethylation to promote genome stability. The binding of GADD45A and ING1b is required for DNA demethylation of methylated reporter plasmids [9]. In many malignancies, GADD45A is down-regulation, which probably allows for the elusion of tumor cells from senescence and apoptosis. Novel approaches are, therefore, being developed to regulate GADD45A levels to combat malignancies.

[1] Fornace A, Nebert D, et al. Mammalian Genes Coordinately Regulated by Growth Arrest Signals and DNA-Damaging Agents [J]. Mol Cell Biol. 1989;9:4196–4203.
[2] Rosemary Siafakas A, Richardson DR. Growth arrest and DNA damage-45 alpha (GADD45alpha) [J]. Int J Biochem Cell Biol. 2009 May;41(5):986-9.
[3] Zhan Q. Gadd45a, a p53- and BRCA1-regulated stress protein, in cellular response to DNA damage [J]. Mutat Res. 2005 Jan 6; 569(1-2):133-43.
[4] Smith ML, Chen IT, et al. Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen [J]. Science. 1994 Nov 25;266(5189):1376-80.
[5] Hollander MC, Fornace AJ. Genomic instability, centrosome amplification, cell cycle checkpoints and Gadd45a [J]. Oncogene. 2002;21:6228–33.
[6] Salvador JM, Brown-Clay JD, et al. Gadd45 in stress signaling, cell cycle control, and apoptosis [J]. Adv Exp Med Biol. 2013; 793:1-19.
[7] Bulavin DV, Kovalsky O, et al. Loss of oncogenic H-ras-induced cell cycle arrest and p38 mitogen-activated protein kinase activation by disruption of Gadd45a [J]. Mol Cell Biol. 2003;23:3859–71.
[8] Hollander MC, Sheikh MS, et al. Genomic instability in Gadd45a-deficient mice [J]. Nat Genet. 1999 Oct;23(2):176-84.
[9] Andrea Schäfer, Emil Karaulanov, et al. Ing1 functions in DNA demethylation by directing Gadd45a to H3K4me3 [J]. Genes & Dev. 2013. 27: 261-273.

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