PMID- 15905878
OWN - NLM
STAT- MEDLINE
DCOM- 20051110
LR  - 20220318
IS  - 1350-9047 (Print)
IS  - 1350-9047 (Linking)
VI  - 12
IP  - 10
DP  - 2005 Oct
TI  - Cell size reduction induced by inhibition of the mTOR/S6K-signaling pathway 
      protects Jurkat cells from apoptosis.
PG  - 1344-57
AB  - In Jurkat cells, the decreased cell growth rate associated with a long-lasting 
      deactivation of the mammalian target of rapamycin (mTOR)/p70 ribosomal S6 kinase 
      (S6K)-signaling pathway generates a cell population of progressively reduced 
      cellular mass and size. When promoted by rapamycin as prototype inhibitor, the 
      mTOR deactivation-dependent cell size reduction was associated with slowed, but 
      not suppressed, proliferation. Small-size cells were significantly protected from 
      apoptosis induced by Fas/Apo-1 death-receptor activation (as shown by reduced 
      procaspase cleavage and decreased catalytic activity of relevant caspases) or by 
      stress signals-dependent mitochondrial perturbation (as shown by reduced cleavage 
      of caspase-2, lower dissipation of mitochondrial membrane potential and decreased 
      release of cytochorome c and apoptosis-inducing factor from mitochondria). 
      Protection faded when reactivation of the mTOR/S6K pathway promoted the cell 
      recovery to normal size. These results suggest that cells induced to reduce their 
      mass by the mTOR deactivation-dependent inhibition of cell growth become more 
      resilient to lethal assaults by curbing the cell's suicidal response.
FAU - Fumarola, C
AU  - Fumarola C
AD  - Department of Experimental Medicine, Division of Molecular Pathology and 
      Immunology. University of Parma, Parma 43100, Italy. claudia.fumarola@unipr.it
FAU - La Monica, S
AU  - La Monica S
FAU - Alfieri, R R
AU  - Alfieri RR
FAU - Borra, E
AU  - Borra E
FAU - Guidotti, G G
AU  - Guidotti GG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Cell Death Differ
JT  - Cell death and differentiation
JID - 9437445
RN  - 0 (Chromones)
RN  - 0 (Cytochrome c Group)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Morpholines)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - GMW67QNF9C (Leucine)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Apoptosis/*physiology
MH  - Cell Growth Processes/physiology
MH  - Cell Size
MH  - Chromones/pharmacology
MH  - Cytochrome c Group/metabolism
MH  - Energy Metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Humans
MH  - Jurkat Cells/*cytology/enzymology/metabolism
MH  - Leucine/metabolism
MH  - Mitochondria/metabolism
MH  - Mitochondrial Proteins/metabolism
MH  - Morpholines/pharmacology
MH  - Phosphorylation
MH  - Protein Kinases/*metabolism/physiology
MH  - Ribosomal Protein S6 Kinases, 70-kDa/*antagonists & inhibitors/metabolism
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases
EDAT- 2005/05/21 09:00
MHDA- 2005/11/11 09:00
CRDT- 2005/05/21 09:00
PHST- 2005/05/21 09:00 [pubmed]
PHST- 2005/11/11 09:00 [medline]
PHST- 2005/05/21 09:00 [entrez]
AID - 4401660 [pii]
AID - 10.1038/sj.cdd.4401660 [doi]
PST - ppublish
SO  - Cell Death Differ. 2005 Oct;12(10):1344-57. doi: 10.1038/sj.cdd.4401660.