Akt phosphorylates and regulates Pdcd4 tumor suppressor protein

Alexey Palamarchuk, Alexey Efanov, Vadim Maximov, Rami I. Aqeilan, Carlo M. Croce, Yuri Pekarsky*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

131 Scopus citations

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 Ser67 and Ser457, we investigated whether Akt phosphorylates and regulates Pdcd4. Our results show that Akt specifically phosphorylates Ser67 and Ser457 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.

Original languageAmerican English
Pages (from-to)11282-11286
Number of pages5
JournalCancer Research
Volume65
Issue number24
DOIs
StatePublished - 15 Dec 2005
Externally publishedYes

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