Nowosad, A;
Besson, A;
(2020)
CDKN1B/p27 regulates autophagy via the control of Ragulator and MTOR activity in amino acid-deprived cells.
Autophagy
, 16
(12)
pp. 2297-2298.
10.1080/15548627.2020.1831217.
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CDKN1B p27 regulates autophagy via the control of Ragulator and MTOR activity in amino acid deprived cells.pdf - Accepted Version Download (776kB) | Preview |
Abstract
The tumor suppressor CDKN1B/p27Kip1 binds to and inhibits cyclin-CDK complexes in the nucleus, inducing cell cycle arrest. However, when in the cytoplasm, CDKN1B may promote tumorigenesis. Notably, cytoplasmic CDKN1B was reported to promote macroautophagy/autophagy in response to nutrient shortage by a previously unknown mechanism. In our recent work, we found that during prolonged amino acid starvation, CDKN1B promotes autophagy via an MTORC1-dependent pathway. A fraction of CDKN1B translocates to lysosomes, where it interacts with the Ragulator subunit LAMTOR1, preventing Ragulator assembly, which is required for MTORC1 activation in response to amino acids. Therefore, CDKN1B represses MTORC1 activity, leading to nuclear translocation of the transcription factor TFEB and activation of lysosomal function, enhancing starvation-induced autophagy flux and apoptosis. In contrast, cells lacking CDKN1B survive starvation despite reduced autophagy, due to elevated MTORC1 activation. These findings reveal that, by directly repressing MTORC1 activity, CDKN1B couples the cell cycle and cell growth machineries during metabolic stress.
Type: | Article |
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Title: | CDKN1B/p27 regulates autophagy via the control of Ragulator and MTOR activity in amino acid-deprived cells |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1080/15548627.2020.1831217 |
Publisher version: | https://doi.org/10.1080/15548627.2020.1831217 |
Language: | English |
Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
Keywords: | CDKN1B/p27/Kip1, mTOR, Ragulator, LAMTOR1, autophagy, cell growth, cell cycle |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio |
URI: | https://discovery.ucl.ac.uk/id/eprint/10114254 |
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