Cancer Res. 2005 Dec 15;65(24):11282-6.

Akt phosphorylates and regulates Pdcd4 tumor suppressor protein.

Palamarchuk A, Efanov A, Maximov V, Aqeilan RI, Croce CM, Pekarsky Y.

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Comprehensive Cancer Center, Human Cancer Genetics Program, and Department of Molecular Virology, Immunology, and Medical Genetics, Ohio State University School of Medicine, Columbus, 43210, USA.

Abstract

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.

PMID:: 16357133; [PubMed - indexed for MEDLINE]

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