Growth arrest and DNA damage-inducible protein alpha (GADD45A)

Growth arrest and DNA damage-inducible protein alpha (GADD45A) is a critical stress-sensor protein that maintains genomic stability by linking DNA damage signals to cell cycle arrest, DNA repair, and apoptosis (UniProt P24522). It is primarily localized in the nucleus and is transcriptionally regulated by p53-dependent and independent pathways in response to ionizing radiation, UV light, and genotoxic stress (NCBI Gene ID: 1647). GADD45A exerts its tumor-suppressive effects by inhibiting the CDK1/Cyclin B1 complex to induce G2/M arrest and by interacting with Proliferating Cell Nuclear Antigen (PCNA) to facilitate nucleotide excision repair (PubMed: 10866302). In many human malignancies, GADD45A expression is frequently downregulated, which correlates with increased genomic instability and poor prognosis (PubMed: 25103565). While not a traditional receptor, it is a key target for therapeutic strategies aimed at restoring its function or utilizing its induction as a biomarker for genotoxicity in drug development (PubMed: 17439431). Current research explores the use of GADD45A-mimetic peptides and small molecules to sensitize cancer cells to chemotherapy and radiation (PubMed: 22431510).

Other names

GADD45DNA damage-inducible transcript 1DDIT1Gadd45a

Inhibition of CDK1/Cyclin B1 complex and interaction with PCNA to facilitate DNA repair and cell cycle arrest.