Akt phosphorylates and regulates Pdcd4 tumor suppressor protein

被引:134
作者
Palamarchuk, A
Efanov, A
Maximov, V
Aqeilan, RI
Croce, CM
Pekarsky, Y
机构
[1] Ohio State Univ, Sch Med, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43210 USA
[2] Ohio State Univ, Sch Med, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA
关键词
D O I
10.1158/0008-5472.CAN-05-3469
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Programmed cell death 4 (Pdcd4) is a tumor suppressor protein that interacts with eukaryotic initiation factor 4A and inhibits protein synthesis. Pdcd4 also suppresses the transactivation of activator protein-1 (AP-1)-responsive promoters by c-Jun. The Akt (protein kinase B) serine/threonine kinase is a key mediator of phosphoinositide 3-kinase pathway involved in the regulation of cell proliferation, survival, and growth. Because Pdcd4 has two putative Akt phosphorylation sites at Ser(67) and Ser(457), We investigated whether Akt phosphorylates and regulates Pdcd4. Our results show that Akt specifically phosphorylates Ser(67) and Ser(457) residues of Pdcd4 in vitro and in vivo. We further show that phosphorylation of Pdcd4 by Akt causes nuclear translocation of Pdcd4. Using luciferase assay, we show that phosphorylation of Pdcd4 by Akt also causes a significant decrease of the ability of Pdcd4 to interfere With the transactivation of AP-1-responsive promoter by c-Jun.
引用
收藏
页码:11282 / 11286
页数:5
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