Growth Arrest and DNA-Damage-Inducible Alpha (GADD45A) is a protein encoded by the GADD45A gene in humans. This protein is part of the GADD45 family, which includes GADD45B and GADD45G. These proteins are known for their roles in responding to environmental stresses, such as DNA damage, and are involved in various cellular processes including DNA repair, cell cycle control, and apoptosis . GADD45A is particularly notable for its ability to mediate the activation of the p38/JNK pathway via MTK1/MEKK4 kinase .
The preparation of human recombinant GADD45A involves several steps. Typically, the gene encoding GADD45A is cloned into an expression vector, which is then introduced into a suitable host cell, such as E. coli or yeast. The host cells are cultured under conditions that promote the expression of the recombinant protein. After sufficient growth, the cells are harvested and lysed to release the protein. The recombinant GADD45A is then purified using techniques such as affinity chromatography, which exploits the protein’s specific binding properties to isolate it from other cellular components .
GADD45A plays a crucial role in various biochemical pathways. It is involved in the regulation of the cell cycle and DNA repair mechanisms. One of the key interactions of GADD45A is with the ATP synthase F1 subunit alpha (ATP5A1), where it affects the ubiquitination and degradation of ATP5A1. This interaction leads to decreased ATP synthesis and inactivation of the cAMP/PKA/LKB1 signaling pathway . Additionally, GADD45A has been shown to influence the expression of adipogenic genes, promoting intramuscular preadipocyte adipogenesis .