PMID- 17053147
OWN - NLM
STAT- MEDLINE
DCOM- 20061030
LR  - 20220309
IS  - 1095-9203 (Electronic)
IS  - 0036-8075 (Linking)
VI  - 314
IP  - 5798
DP  - 2006 Oct 20
TI  - S6K1- and betaTRCP-mediated degradation of PDCD4 promotes protein translation and 
      cell growth.
PG  - 467-71
AB  - The tumor suppressor programmed cell death protein 4 (PDCD4) inhibits the 
      translation initiation factor eIF4A, an RNA helicase that catalyzes the unwinding 
      of secondary structure at the 5' untranslated region (5'UTR) of messenger RNAs 
      (mRNAs). In response to mitogens, PDCD4 was rapidly phosphorylated on Ser67 by 
      the protein kinase S6K1 and subsequently degraded via the ubiquitin ligase 
      SCF(betaTRCP). Expression in cultured cells of a stable PDCD4 mutant that is 
      unable to bind betaTRCP inhibited translation of an mRNA with a structured 5'UTR, 
      resulted in smaller cell size, and slowed down cell cycle progression. We propose 
      that regulated degradation of PDCD4 in response to mitogens allows efficient 
      protein synthesis and consequently cell growth.
FAU - Dorrello, N Valerio
AU  - Dorrello NV
AD  - Department of Pathology, NYU Cancer Institute, New York University School of 
      Medicine, 550 First Avenue, MSB 599, New York, NY 10016, USA.
FAU - Peschiaroli, Angelo
AU  - Peschiaroli A
FAU - Guardavaccaro, Daniele
AU  - Guardavaccaro D
FAU - Colburn, Nancy H
AU  - Colburn NH
FAU - Sherman, Nicholas E
AU  - Sherman NE
FAU - Pagano, Michele
AU  - Pagano M
LA  - eng
GR  - R01-CA76584/CA/NCI NIH HHS/United States
GR  - R01-GM57587/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (5' Untranslated Regions)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Eukaryotic Initiation Factor-4F)
RN  - 0 (Eukaryotic Initiation Factor-4G)
RN  - 0 (Eukaryotic Initiation Factors)
RN  - 0 (Mitogens)
RN  - 0 (PDCD4 protein, human)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (beta-Transducin Repeat-Containing Proteins)
RN  - 452VLY9402 (Serine)
RN  - EC 2.3.2.27 (SKP Cullin F-Box Protein Ligases)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.7.- (Eukaryotic Initiation Factor-4A)
SB  - IM
CIN - Science. 2006 Oct 20;314(5798):428-9. PMID: 17053135
MH  - 5' Untranslated Regions
MH  - Amino Acid Motifs
MH  - Apoptosis Regulatory Proteins/chemistry/genetics/*metabolism
MH  - Binding Sites
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - *Cell Proliferation
MH  - Cell Size
MH  - Eukaryotic Initiation Factor-4A/antagonists & inhibitors/metabolism
MH  - Eukaryotic Initiation Factor-4F/metabolism
MH  - Eukaryotic Initiation Factor-4G/metabolism
MH  - Eukaryotic Initiation Factors/metabolism
MH  - Humans
MH  - Mitogens/pharmacology
MH  - Phosphorylation
MH  - *Protein Biosynthesis
MH  - RNA, Small Interfering
MH  - RNA-Binding Proteins/chemistry/genetics/*metabolism
MH  - Ribosomal Protein S6 Kinases/metabolism
MH  - SKP Cullin F-Box Protein Ligases/*metabolism
MH  - Serine/metabolism
MH  - Serum
MH  - Signal Transduction
MH  - beta-Transducin Repeat-Containing Proteins/genetics/*metabolism
EDAT- 2006/10/21 09:00
MHDA- 2006/10/31 09:00
CRDT- 2006/10/21 09:00
PHST- 2006/10/21 09:00 [pubmed]
PHST- 2006/10/31 09:00 [medline]
PHST- 2006/10/21 09:00 [entrez]
AID - 314/5798/467 [pii]
AID - 10.1126/science.1130276 [doi]
PST - ppublish
SO  - Science. 2006 Oct 20;314(5798):467-71. doi: 10.1126/science.1130276.