PMID- 19515765
OWN - NLM
STAT- MEDLINE
DCOM- 20090831
LR  - 20211203
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 83
IP  - 17
DP  - 2009 Sep
TI  - Simian virus 40 small T antigen activates AMPK and triggers autophagy to protect 
      cancer cells from nutrient deprivation.
PG  - 8565-74
LID - 10.1128/JVI.00603-09 [doi]
AB  - As tumors grow larger, they often experience an insufficient supply of oxygen and 
      nutrients. Hence, cancer cells must develop mechanisms to overcome these 
      stresses. Using an in vitro transformation model where the presence of the simian 
      virus 40 (SV40) small T (ST) antigen has been shown to be critical for 
      tumorigenic transformation, we investigated whether the ST antigen has a role to 
      play in regulating the energy homeostasis of cancer cells. We find that cells 
      expressing the SV40 ST antigen (+ST cells) are more resistant to glucose 
      deprivation-induced cell death than cells lacking the SV40 ST antigen (-ST 
      cells). Mechanistically, we find that the ST antigen mediates this effect by 
      activating a nutrient-sensing kinase, AMP-activated protein kinase (AMPK). The 
      basal level of active, phosphorylated AMPK was higher in +ST cells than in -ST 
      cells, and these levels increased further in response to glucose deprivation. 
      Additionally, inhibition of AMPK in +ST cells increased the rate of cell death, 
      while activation of AMPK in -ST cells decreased the rate of cell death, under 
      conditions of glucose deprivation. We further show that AMPK mediates its 
      effects, at least in part, by inhibiting mTOR (mammalian target of rapamycin), 
      thereby shutting down protein translation. Finally, we show that +ST cells 
      exhibit a higher percentage of autophagy than -ST cells upon glucose deprivation. 
      Thus, we demonstrate a novel role for the SV40 ST antigen in cancers, where it 
      functions to maintain energy homeostasis during glucose deprivation by activating 
      AMPK, inhibiting mTOR, and inducing autophagy as an alternate energy source.
FAU - Kumar, Sravanth Hindupur
AU  - Kumar SH
AD  - Department of Molecular Reproduction, Development, and Genetics, Indian Institute 
      of Science, Bangalore 560012, India.
FAU - Rangarajan, Annapoorni
AU  - Rangarajan A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090610
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Antigens, Polyomavirus Transforming)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - AMP-Activated Protein Kinases/*biosynthesis
MH  - Antigens, Polyomavirus Transforming/*physiology
MH  - *Autophagy
MH  - Cell Death
MH  - Cell Line
MH  - Glucose/metabolism
MH  - Humans
MH  - Protein Kinases/metabolism
MH  - Simian virus 40/*physiology
MH  - TOR Serine-Threonine Kinases
PMC - PMC2738183
EDAT- 2009/06/12 09:00
MHDA- 2009/09/01 06:00
PMCR- 2010/03/01
CRDT- 2009/06/12 09:00
PHST- 2009/06/12 09:00 [entrez]
PHST- 2009/06/12 09:00 [pubmed]
PHST- 2009/09/01 06:00 [medline]
PHST- 2010/03/01 00:00 [pmc-release]
AID - JVI.00603-09 [pii]
AID - 0603-09 [pii]
AID - 10.1128/JVI.00603-09 [doi]
PST - ppublish
SO  - J Virol. 2009 Sep;83(17):8565-74. doi: 10.1128/JVI.00603-09. Epub 2009 Jun 10.