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.

Cell size reduction induced by inhibition of the mTOR/S6K signaling pathway protects Jurkat cells from apoptosis / Fumarola, Claudia; LA MONICA, Silvia; Alfieri, Roberta; Borra, Elena; Guidotti, G. G.. - In: CELL DEATH AND DIFFERENTIATION. - ISSN 1350-9047. - 12:(2005), pp. 1344-1357. [10.1038/sj.cdd.4401660]

Cell size reduction induced by inhibition of the mTOR/S6K signaling pathway protects Jurkat cells from apoptosis

FUMAROLA, Claudia;LA MONICA, Silvia;ALFIERI, Roberta;BORRA, Elena;
2005-01-01

Abstract

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.
2005
Cell size reduction induced by inhibition of the mTOR/S6K signaling pathway protects Jurkat cells from apoptosis / Fumarola, Claudia; LA MONICA, Silvia; Alfieri, Roberta; Borra, Elena; Guidotti, G. G.. - In: CELL DEATH AND DIFFERENTIATION. - ISSN 1350-9047. - 12:(2005), pp. 1344-1357. [10.1038/sj.cdd.4401660]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/1445408
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