GADD45A (growth arrest and DNA-damage-inducible, alpha)
Atlas of Genetics and Cytogenetics in Oncology and Haematology
Growth Arrest and DNA-damage-inducible, alpha (GADD45α) is a member of the GADD family proteins that also include GADD45β and GADD45γ. The highly conserved GADD45 proteins are small (18 kDa) and primarily localized in the nucleus. The GADD45 proteins acting as sensors of environmental and physiological stress interact with and/or modulate the activities of partner proteins involved in cell cycle, cell survival, apoptosis, maintenance of genomic stability and DNA repair. GADD45 proteins also act
... 5 proteins also act as sensors of oncogenic stress in the initiation of tumors and in tumor responses to different therapeutics. The expression of GADD45α in response to DNA damage is mediated by p53-dependent and p53independent mechanisms, the latter which involves Wilms tumor 1 (WT1) protein. GADD45α subsequently inhibits G2/M transition of cell cycle and induces apoptosis. GADD45α also has a role in DNA-demethylation to promote genome stability. In many malignancies, GADD45α levels are downregulated, likely allowing tumor cells to escape from senescence and apoptosis. Novel approaches are therefore being developed to regulate GADD45α levels to combat malignancies.