A splice variant of stress response gene ATF3 counteracts NF-kappa B-dependent anti-apoptosis through inhibiting recruitment of CREB-binding protein/p300 coactivator

作者：Hua B; Tamamori Adachi M; Luo Y; Tamura K; Morioka M; Fukuda M; Tanaka Y; Kitajima S^*

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281(3): 1620-1629.

DOI：10.1074/jbc.M508471200

Activating transcription factor (ATF) 3 plays a role in determining cell fate and generates a variety of alternatively spliced isoforms in stress response. We have reported previously that splice variant ATF3 Delta Zip2, which lacks the leucine zipper region, is induced in response to various stress stimuli. However, its biological function has not been elucidated. By using cells treated with tumor necrosis factor-alpha and actinomycin D or cells overexpressing ATF3 Delta Zip2, we showed that ATF3 Delta Zip2 sensitizes cells to apoptotic cell death in response to tumor necrosis factor-alpha, at least in part through suppressing nuclear factor (NF)-kappa B-dependent transcription of antiapoptotic genes such as cIAP2 and XIAP. ATF3 Delta Zip2 interacts with a p65 (RelA)-cofactor complex containing CBP/p300 and HDAC1 at NF-kappa B sites of the proximal promoter region of the cIAP2 gene in vivo and down-regulates the recruitment of CBP/p300. Our study revealed that ATF3 Delta Zip2 counteracts anti-apoptotic activity of NF-kappa B, at least in part, by displacing positive cofactor CBP/p300 and provides insight into the mechanism by which ATF3 regulates cell fate through alternative splicing in stress response.

• 出版日期2006-1-20