S phase-coupled E2f1 destruction ensures homeostasis in proliferating tissues.

Precise control of cell cycle regulators is critical for normal development and tissue homeostasis. E2F transcription factors are activated during G1 to drive the G1-S transition and are then inhibited during S phase by a variety of mechanisms. Here, we genetically manipulate the single Drosophila a...

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Autores principales:	Jean M Davidson, Robert J Duronio
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/96518a5742d54337b65c3653f1b058b1
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spelling	oai:doaj.org-article:96518a5742d54337b65c3653f1b058b12021-11-18T06:18:14ZS phase-coupled E2f1 destruction ensures homeostasis in proliferating tissues.1553-73901553-740410.1371/journal.pgen.1002831https://doaj.org/article/96518a5742d54337b65c3653f1b058b12012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22916021/pdf/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Precise control of cell cycle regulators is critical for normal development and tissue homeostasis. E2F transcription factors are activated during G1 to drive the G1-S transition and are then inhibited during S phase by a variety of mechanisms. Here, we genetically manipulate the single Drosophila activator E2F (E2f1) to explore the developmental requirement for S phase-coupled E2F down-regulation. Expression of an E2f1 mutant that is not destroyed during S phase drives cell cycle progression and causes apoptosis. Interestingly, this apoptosis is not exclusively the result of inappropriate cell cycle progression, because a stable E2f1 mutant that cannot function as a transcription factor or drive cell cycle progression also triggers apoptosis. This observation suggests that the inappropriate presence of E2f1 protein during S phase can trigger apoptosis by mechanisms that are independent of E2F acting directly at target genes. The ability of S phase-stabilized E2f1 to trigger apoptosis requires an interaction between E2f1 and the Drosophila pRb homolog, Rbf1, and involves induction of the pro-apoptotic gene, hid. Simultaneously blocking E2f1 destruction during S phase and inhibiting the induction of apoptosis results in tissue overgrowth and lethality. We propose that inappropriate accumulation of E2f1 protein during S phase triggers the elimination of potentially hyperplastic cells via apoptosis in order to ensure normal development of rapidly proliferating tissues.Jean M DavidsonRobert J DuronioPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 8, Iss 8, p e1002831 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Jean M Davidson Robert J Duronio S phase-coupled E2f1 destruction ensures homeostasis in proliferating tissues.
description	Precise control of cell cycle regulators is critical for normal development and tissue homeostasis. E2F transcription factors are activated during G1 to drive the G1-S transition and are then inhibited during S phase by a variety of mechanisms. Here, we genetically manipulate the single Drosophila activator E2F (E2f1) to explore the developmental requirement for S phase-coupled E2F down-regulation. Expression of an E2f1 mutant that is not destroyed during S phase drives cell cycle progression and causes apoptosis. Interestingly, this apoptosis is not exclusively the result of inappropriate cell cycle progression, because a stable E2f1 mutant that cannot function as a transcription factor or drive cell cycle progression also triggers apoptosis. This observation suggests that the inappropriate presence of E2f1 protein during S phase can trigger apoptosis by mechanisms that are independent of E2F acting directly at target genes. The ability of S phase-stabilized E2f1 to trigger apoptosis requires an interaction between E2f1 and the Drosophila pRb homolog, Rbf1, and involves induction of the pro-apoptotic gene, hid. Simultaneously blocking E2f1 destruction during S phase and inhibiting the induction of apoptosis results in tissue overgrowth and lethality. We propose that inappropriate accumulation of E2f1 protein during S phase triggers the elimination of potentially hyperplastic cells via apoptosis in order to ensure normal development of rapidly proliferating tissues.
format	article
author	Jean M Davidson Robert J Duronio
author_facet	Jean M Davidson Robert J Duronio
author_sort	Jean M Davidson
title	S phase-coupled E2f1 destruction ensures homeostasis in proliferating tissues.
title_short	S phase-coupled E2f1 destruction ensures homeostasis in proliferating tissues.
title_full	S phase-coupled E2f1 destruction ensures homeostasis in proliferating tissues.
title_fullStr	S phase-coupled E2f1 destruction ensures homeostasis in proliferating tissues.
title_full_unstemmed	S phase-coupled E2f1 destruction ensures homeostasis in proliferating tissues.
title_sort	s phase-coupled e2f1 destruction ensures homeostasis in proliferating tissues.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/96518a5742d54337b65c3653f1b058b1
work_keys_str_mv	AT jeanmdavidson sphasecouplede2f1destructionensureshomeostasisinproliferatingtissues AT robertjduronio sphasecouplede2f1destructionensureshomeostasisinproliferatingtissues
_version_	1718424495290580992

S phase-coupled E2f1 destruction ensures homeostasis in proliferating tissues.

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