Akt phosphorylates and regulates Pdcd4 tumor suppressor protein

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...

Full description

Saved in:
Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2005-12, Vol.65 (24), p.11282-11286
Main Authors: PALAMARCHUK, Alexey, EFANOV, Alexey, MAXIMOV, Vadim, AQEILAN, Rami I, CROCE, Carlo M, PEKARSKY, Yuri
Format: Article
Language:English
Subjects:
Apoptosis Regulatory Proteins - genetics
Apoptosis Regulatory Proteins - metabolism
Biological and medical sciences
Cell Nucleus - metabolism
Cell physiology
Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
Cells, Cultured
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation
Humans
Kidney - metabolism
Luciferases - metabolism
Molecular and cellular biology
Phosphatidylinositol 3-Kinases - metabolism
Phosphorylation
Promoter Regions, Genetic
Protein Transport
Proto-Oncogene Proteins c-akt - metabolism
Proto-Oncogene Proteins c-jun - metabolism
RNA-Binding Proteins - genetics
RNA-Binding Proteins - metabolism
Serine - chemistry
Serine - genetics
Transcription Factor AP-1 - metabolism
Transcriptional Activation
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.can-05-3469