Strategic cell-cycle regulatory features that provide mammalian cells with tunable G1 length and reversible G1 arrest.

Transitions between consecutive phases of the eukaryotic cell cycle are driven by the catalytic activity of selected sets of cyclin-dependent kinases (Cdks). Yet, their occurrence and precise timing is tightly scheduled by a variety of means including Cdk association with inhibitory/adaptor proteins...

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Autor principal:	Benjamin Pfeuty
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/26ec3abe1fed48fcbc996d3cd5077712
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spelling	oai:doaj.org-article:26ec3abe1fed48fcbc996d3cd50777122021-11-18T07:21:12ZStrategic cell-cycle regulatory features that provide mammalian cells with tunable G1 length and reversible G1 arrest.1932-620310.1371/journal.pone.0035291https://doaj.org/article/26ec3abe1fed48fcbc996d3cd50777122012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22558136/?tool=EBIhttps://doaj.org/toc/1932-6203Transitions between consecutive phases of the eukaryotic cell cycle are driven by the catalytic activity of selected sets of cyclin-dependent kinases (Cdks). Yet, their occurrence and precise timing is tightly scheduled by a variety of means including Cdk association with inhibitory/adaptor proteins (CKIs). Here we focus on the regulation of G1-phase duration by the end of which cells of multicelled organisms must decide whether to enter S phase or halt, and eventually then, differentiate, senesce or die to obey the homeostatic rules of their host. In mammalian cells, entry in and progression through G1 phase involve sequential phosphorylation and inactivation of the retinoblastoma Rb proteins, first, by cyclin D-Cdk4,6 with the help of CKIs of the Cip/Kip family and, next, by the cyclin E-Cdk2 complexes that are negatively regulated by Cip/Kip proteins. Using a dynamical modeling approach, we show that the very way how the Rb and Cip/Kip regulatory modules interact differentially with cyclin D-Cdk4,6 and cyclin E-Cdk2 provides to mammalian cells a powerful means to achieve an exquisitely-sensitive control of G1-phase duration and fully reversible G1 arrests. Consistently, corruption of either one of these two modules precludes G1 phase elongation and is able to convert G1 arrests from reversible to irreversible. This study unveils fundamental design principles of mammalian G1-phase regulation that are likely to confer to mammalian cells the ability to faithfully control the occurrence and timing of their division process in various conditions.Benjamin PfeutyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e35291 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Benjamin Pfeuty Strategic cell-cycle regulatory features that provide mammalian cells with tunable G1 length and reversible G1 arrest.
description	Transitions between consecutive phases of the eukaryotic cell cycle are driven by the catalytic activity of selected sets of cyclin-dependent kinases (Cdks). Yet, their occurrence and precise timing is tightly scheduled by a variety of means including Cdk association with inhibitory/adaptor proteins (CKIs). Here we focus on the regulation of G1-phase duration by the end of which cells of multicelled organisms must decide whether to enter S phase or halt, and eventually then, differentiate, senesce or die to obey the homeostatic rules of their host. In mammalian cells, entry in and progression through G1 phase involve sequential phosphorylation and inactivation of the retinoblastoma Rb proteins, first, by cyclin D-Cdk4,6 with the help of CKIs of the Cip/Kip family and, next, by the cyclin E-Cdk2 complexes that are negatively regulated by Cip/Kip proteins. Using a dynamical modeling approach, we show that the very way how the Rb and Cip/Kip regulatory modules interact differentially with cyclin D-Cdk4,6 and cyclin E-Cdk2 provides to mammalian cells a powerful means to achieve an exquisitely-sensitive control of G1-phase duration and fully reversible G1 arrests. Consistently, corruption of either one of these two modules precludes G1 phase elongation and is able to convert G1 arrests from reversible to irreversible. This study unveils fundamental design principles of mammalian G1-phase regulation that are likely to confer to mammalian cells the ability to faithfully control the occurrence and timing of their division process in various conditions.
format	article
author	Benjamin Pfeuty
author_facet	Benjamin Pfeuty
author_sort	Benjamin Pfeuty
title	Strategic cell-cycle regulatory features that provide mammalian cells with tunable G1 length and reversible G1 arrest.
title_short	Strategic cell-cycle regulatory features that provide mammalian cells with tunable G1 length and reversible G1 arrest.
title_full	Strategic cell-cycle regulatory features that provide mammalian cells with tunable G1 length and reversible G1 arrest.
title_fullStr	Strategic cell-cycle regulatory features that provide mammalian cells with tunable G1 length and reversible G1 arrest.
title_full_unstemmed	Strategic cell-cycle regulatory features that provide mammalian cells with tunable G1 length and reversible G1 arrest.
title_sort	strategic cell-cycle regulatory features that provide mammalian cells with tunable g1 length and reversible g1 arrest.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/26ec3abe1fed48fcbc996d3cd5077712
work_keys_str_mv	AT benjaminpfeuty strategiccellcycleregulatoryfeaturesthatprovidemammaliancellswithtunableg1lengthandreversibleg1arrest
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Strategic cell-cycle regulatory features that provide mammalian cells with tunable G1 length and reversible G1 arrest.

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