A Systems Biology Approach Identifies Hidden Regulatory Connections Between the Circadian and Cell-Cycle Checkpoints.
checkpoint signaling
circadian rhythms
clock genes
mathematical modeling
p53
systematic approach
tumor suppressor
Journal
Frontiers in physiology
ISSN: 1664-042X
Titre abrégé: Front Physiol
Pays: Switzerland
ID NLM: 101549006
Informations de publication
Date de publication:
2020
2020
Historique:
received:
03
02
2020
accepted:
20
03
2020
entrez:
7
5
2020
pubmed:
7
5
2020
medline:
7
5
2020
Statut:
epublish
Résumé
Circadian rhythms form a self-sustaining, endogenous, time-keeping system that allows organisms to anticipate daily environmental changes. The core of the clock network consists of interlocking transcriptional-translational feedback loops that ensures that metabolic, behavioral, and physiological processes run on a 24 h timescale. The hierarchical nature of the clock manifests itself in multiple points of control on the daily cell division cycle, which relies on synthesis, degradation, and post-translational modification for progression. This relationship is particularly important for understanding the role of clock components in sensing stress conditions and triggering checkpoint signals that stop cell cycle progression. A case in point is the interplay among the circadian factor PERIOD2 (PER2), the tumor suppressor p53, and the oncogenic mouse double minute-2 homolog protein (MDM2), which is the p53's negative regulator. Under unstressed conditions, PER2 and p53 form a stable complex in the cytosol and, along with MDM2, a trimeric complex in the nucleus. Association of PER2 to the C-terminus end of p53 prevents MDM2-mediated ubiquitylation and degradation of p53 as well as p53's transcriptional activation. Remarkably, when not bound to p53, PER2 acts as substrate for the E3-ligase activity of MDM2; thus, PER2 is degraded in a phosphorylation-independent fashion. Unexpectedly, the phase relationship between PER2 and p53 are opposite; however, a systematic modeling approach, inferred from the oscillatory time course data of PER2 and p53, aided in identifying additional regulatory scenarios that explained,
Identifiants
pubmed: 32372973
doi: 10.3389/fphys.2020.00327
pmc: PMC7176909
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
327Informations de copyright
Copyright © 2020 Zou, Kim, Gotoh, Liu, Kim and Finkielstein.
Références
Mol Cell Biol. 2005 Apr;25(7):2795-807
pubmed: 15767683
Biophys J. 2014 Aug 5;107(3):783-793
pubmed: 25099817
Science. 2012 Oct 19;338(6105):349-54
pubmed: 22936566
Sci Signal. 2009 Jun 02;2(73):ra26
pubmed: 19491384
J Biol Rhythms. 2012 Jun;27(3):226-36
pubmed: 22653891
Nat Rev Genet. 2005 Jul;6(7):544-56
pubmed: 15951747
Cell. 1998 Jul 10;94(1):83-95
pubmed: 9674430
J Pharmacol Exp Ther. 2007 Aug;322(2):730-8
pubmed: 17502429
Trends Cell Biol. 2018 May;28(5):368-379
pubmed: 29471986
Cell Death Differ. 2010 Feb;17(2):255-67
pubmed: 19927155
Cell. 2004 Nov 24;119(5):693-705
pubmed: 15550250
Proc Natl Acad Sci U S A. 2012 Jan 3;109(1):101-6
pubmed: 22184224
Cell Cycle. 2011 Nov 1;10(21):3788-97
pubmed: 22033214
Nat Commun. 2013;4:2444
pubmed: 24051492
Mol Cell. 2015 Oct 1;60(1):77-88
pubmed: 26431025
Proc Natl Acad Sci U S A. 2016 Nov 22;113(47):13516-13521
pubmed: 27834218
Elife. 2015 Mar 10;4:
pubmed: 25756610
Trends Mol Med. 2016 Jan;22(1):68-81
pubmed: 26691298
Nature. 2005 Mar 31;434(7033):640-4
pubmed: 15800623
Am J Pathol. 2001 May;158(5):1793-801
pubmed: 11337377
J Biol Chem. 2008 Feb 22;283(8):4535-42
pubmed: 18086663
Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20746-51
pubmed: 19104043
Cell. 2009 May 1;137(3):413-31
pubmed: 19410540
Proc Natl Acad Sci U S A. 2014 Jan 28;111(4):1397-402
pubmed: 24474764
Mol Cell. 2006 May 5;22(3):375-82
pubmed: 16678109
Mol Cell Biol. 2005 Apr;25(8):3109-16
pubmed: 15798197
IET Syst Biol. 2016 Aug;10(4):125-35
pubmed: 27444022
Mol Cell. 2016 Nov 17;64(4):774-789
pubmed: 27840026
Proc Natl Acad Sci U S A. 2018 Jun 5;115(23):5986-5991
pubmed: 29784789
Cell. 1998 Jul 10;94(1):97-107
pubmed: 9674431
Cell. 2009 Oct 2;139(1):199-210
pubmed: 19765810
Curr Biol. 2017 Nov 20;27(22):3454-3467.e8
pubmed: 29103939
Nat Rev Mol Cell Biol. 2007 Feb;8(2):139-48
pubmed: 17245414
J Biol Chem. 2005 Aug 19;280(33):29397-402
pubmed: 15972822
Mol Syst Biol. 2019 Jul;15(7):e8838
pubmed: 31353796
J Invest Dermatol. 1991 Aug;97(2):273-80
pubmed: 1830075
FEBS Lett. 2011 May 20;585(10):1393-9
pubmed: 21376720
Am J Pathol. 1999 Feb;154(2):613-22
pubmed: 10027418
Science. 2010 Mar 19;327(5972):1522-6
pubmed: 20299597
Proc Natl Acad Sci U S A. 2013 Jan 29;110(5):1592-9
pubmed: 23267082
Proc Natl Acad Sci U S A. 2011 Sep 27;108(39):16451-6
pubmed: 21930935
Mol Syst Biol. 2012;8:630
pubmed: 23212247
Nat Rev Genet. 2017 Mar;18(3):164-179
pubmed: 27990019
Nat Commun. 2015 Nov 30;6:8587
pubmed: 26617050
Drug Resist Updat. 2003 Dec;6(6):313-22
pubmed: 14744495
Cell. 2011 Apr 29;145(3):357-70
pubmed: 21514639
J Pharmacol Exp Ther. 2009 Aug;330(2):430-9
pubmed: 19458106
Sci Signal. 2018 Nov 13;11(556):
pubmed: 30425162
Mol Cell. 2016 Dec 1;64(5):900-912
pubmed: 27867006
J Biochem. 2008 Nov;144(5):609-18
pubmed: 18782782
CPT Pharmacometrics Syst Pharmacol. 2013 Jul 17;2:e57
pubmed: 23863866
Mol Biol Cell. 2014 Oct 1;25(19):3081-93
pubmed: 25103245
Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15240-5
pubmed: 20696890
Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10183-8
pubmed: 8816773
Science. 2000 Apr 21;288(5465):483-92
pubmed: 10775102
Cell. 2009 May 15;137(4):609-22
pubmed: 19450511
Cold Spring Harb Perspect Biol. 2018 Aug 1;10(8):
pubmed: 29038116
Mol Biol Cell. 2015 Jan 15;26(2):359-72
pubmed: 25411341
Science. 2003 Oct 10;302(5643):255-9
pubmed: 12934012