PMID- 15890927
OWN - NLM
STAT- MEDLINE
DCOM- 20050614
LR  - 20220401
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 79
IP  - 11
DP  - 2005 Jun
TI  - Effects of simian virus 40 large and small tumor antigens on mammalian target of 
      rapamycin signaling: small tumor antigen mediates hypophosphorylation of 
      eIF4E-binding protein 1 late in infection.
PG  - 6882-9
AB  - We report that late in a simian virus 40 (SV40) infection in CV-1 cells, there 
      are significant decreases in phosphorylations of two mammalian target of 
      rapamycin (mTOR) signaling effectors, the eIF4E-binding protein (4E-BP1) and p70 
      S6 kinase (p70S6K). The hypophosphorylation of 4E-BP1 results in 4E-BP1 binding 
      to eIF4E, leading to the inhibition of cap-dependent translation. The 
      dephosphorylation of 4E-BP1 is specifically mediated by SV40 small t antigen and 
      requires the protein phosphatase 2A binding domain but not an active DnaJ domain. 
      Serum-starved primary African green monkey kidney (AGMK) cells also showed 
      decreased phosphorylations of mTOR, 4E-BP1, and p70S6K at late times in infection 
      (48 h postinfection [hpi]). However, at earlier times (12 and 24 hpi), in AGMK 
      cells, phosphorylated p70S6K was moderately increased, correlating with a 
      significant increase in phosphorylation of the p70S6K substrate, ribosomal 
      protein S6. Hyperphosphorylation of 4E-BP1 at early times could not be 
      determined, since hyperphosphorylated 4E-BP1 was present in mock-infected AGMK 
      cells. Elevated levels of phosphorylated eIF4G, a third mTOR effector, were 
      detected in both CV-1 and AGMK cells at all times after infection, indicating 
      that eIF4G phosphorylation was induced throughout the infection and unaffected by 
      small t antigen. The data suggest that during SV40 lytic infection in monkey 
      cells, the phosphorylations of p70S6K, S6, and eIF4G are increased early in the 
      infection (12 and 24 hpi), but late in the infection (48 hpi), the 
      phosphorylations of mTOR, p70S6K, and 4E-BP1 are dramatically decreased by a 
      mechanism mediated, at least in part, by small t antigen.
FAU - Yu, Yongjun
AU  - Yu Y
AD  - Department of Cancer Biology, Abramson Family Cancer Research Institute, 
      University of Pennsylvania, Philadelphia, PA 19104-6142, USA.
FAU - Kudchodkar, Sagar B
AU  - Kudchodkar SB
FAU - Alwine, James C
AU  - Alwine JC
LA  - eng
GR  - R01 CA028379/CA/NCI NIH HHS/United States
GR  - R01 CA28379-25/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Antigens, Polyomavirus Transforming)
RN  - 0 (Capsid Proteins)
RN  - 0 (Carrier Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Ribosomal Protein S6)
RN  - 0 (VP1 protein, polyomavirus)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Antigens, Polyomavirus Transforming/genetics/*physiology
MH  - Capsid Proteins/biosynthesis
MH  - Carrier Proteins/*metabolism
MH  - Cell Line
MH  - Chlorocebus aethiops
MH  - Mutation
MH  - Phosphoproteins/*metabolism
MH  - Phosphorylation
MH  - Protein Biosynthesis
MH  - Protein Kinases/*metabolism
MH  - Ribosomal Protein S6/metabolism
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - Signal Transduction
MH  - Simian virus 40/genetics/*immunology/*pathogenicity/physiology
MH  - TOR Serine-Threonine Kinases
PMC - PMC1112164
EDAT- 2005/05/14 09:00
MHDA- 2005/06/15 09:00
PMCR- 2005/06/01
CRDT- 2005/05/14 09:00
PHST- 2005/05/14 09:00 [pubmed]
PHST- 2005/06/15 09:00 [medline]
PHST- 2005/05/14 09:00 [entrez]
PHST- 2005/06/01 00:00 [pmc-release]
AID - 79/11/6882 [pii]
AID - 2954-04 [pii]
AID - 10.1128/JVI.79.11.6882-6889.2005 [doi]
PST - ppublish
SO  - J Virol. 2005 Jun;79(11):6882-9. doi: 10.1128/JVI.79.11.6882-6889.2005.