Post translational regulation of apoptosis inhibitor 5 api5 during cell cycle progression and dna damage induced apoptosis

Abstract

Apoptosis inhibitor 5 Api5 a known anti apoptotic protein is responsible for inhibition of cell death in stressful conditions like serum starvation and DNA damage Acetylation at K251 is the only known post translational modification that is responsible for maintaining the stability of Api5 However the enzymes involved in the regulation of acetylation and de acetylation of Api5 is yet to be discovered Our studies demonstrate that p300 histone acetyltransferase and HDAC1 are the enzymes that regulate K251 acetylation mediated stability of Api5 The de acetylated and unstable form of Api5 localises to the cytoplasm for proteasomal degradation Api5 undergoes ubiquitination by FBXO3 FBXO6 and FBXW2 prior to post translational degradation through the proteasomal pathway Api5 protein levels have been observed to fluctuate during cell cycle progression Reduced protein expression of Api5 in the G2 M phase of the cell cycle indicate Api5 to undergo cell cycle dependent post translational degradation However the pathway and mechanism for this degradation have not been elucidated We concluded that cell cycle dependent degradation of Api5 is also through the proteasomal pathway This post translational degradation of Api5 in the G2 M phase required Aurora kinase B activity We also investigated the role of post translational modifications of Api5 during DNA damage induced apoptosis We observed Api5 inhibits DNA damage induced apoptosis Once the apoptotic cascade is initiated upon extensive DNA damage Api5 undergoes proteasomal degradation This study also revealed ATR to regulate Api5 upon DNA damage induced apoptosis newline newline