Cargando…

FoxM1, a Forkhead Transcription Factor Is a Master Cell Cycle Regulator for Mouse Mature T Cells but Not Double Positive Thymocytes

FoxM1 is a forkhead box transcription factor and a known master regulator required for different phases of the cell cycle. In cell lines, FoxM1 deficient cells exhibit delayed S phase entry, aneuploidy, polyploidy and can't complete mitosis. In vivo, FoxM1 is expressed mostly in proliferating c...

Descripción completa

Detalles Bibliográficos
Autores principales: Xue, Ling, Chiang, Leslie, He, Bo, Zhao, You-Yang, Winoto, Astar
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2821927/
https://www.ncbi.nlm.nih.gov/pubmed/20169079
http://dx.doi.org/10.1371/journal.pone.0009229
_version_ 1782177478470533120
author Xue, Ling
Chiang, Leslie
He, Bo
Zhao, You-Yang
Winoto, Astar
author_facet Xue, Ling
Chiang, Leslie
He, Bo
Zhao, You-Yang
Winoto, Astar
author_sort Xue, Ling
collection PubMed
description FoxM1 is a forkhead box transcription factor and a known master regulator required for different phases of the cell cycle. In cell lines, FoxM1 deficient cells exhibit delayed S phase entry, aneuploidy, polyploidy and can't complete mitosis. In vivo, FoxM1 is expressed mostly in proliferating cells but is surprisingly also found in non-proliferating CD4(+)CD8(+) double positive thymocytes. Here, we addressed the role of FoxM1 in T cell development by generating and analyzing two different lines of T-cell specific FoxM1 deficient mice. As expected, FoxM1 is required for proliferation of early thymocytes and activated mature T cells. Defective expression of many cell cycle proteins was detected, including cyclin A, cyclin B1, cdc2, cdk2, p27 and the Rb family members p107 and p130 but surprisingly not survivin. Unexpectedly, loss of FoxM1 only affects a few cell cycle proteins in CD4(+)CD8(+) thymocytes and has little effect on their sensitivity to apoptosis and the subsequent steps of T cell differentiation. Thus, regulation of cell cycle genes by FoxM1 is stage- and context-dependent.
format Text
id pubmed-2821927
institution National Center for Biotechnology Information
language English
publishDate 2010
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-28219272010-02-19 FoxM1, a Forkhead Transcription Factor Is a Master Cell Cycle Regulator for Mouse Mature T Cells but Not Double Positive Thymocytes Xue, Ling Chiang, Leslie He, Bo Zhao, You-Yang Winoto, Astar PLoS One Research Article FoxM1 is a forkhead box transcription factor and a known master regulator required for different phases of the cell cycle. In cell lines, FoxM1 deficient cells exhibit delayed S phase entry, aneuploidy, polyploidy and can't complete mitosis. In vivo, FoxM1 is expressed mostly in proliferating cells but is surprisingly also found in non-proliferating CD4(+)CD8(+) double positive thymocytes. Here, we addressed the role of FoxM1 in T cell development by generating and analyzing two different lines of T-cell specific FoxM1 deficient mice. As expected, FoxM1 is required for proliferation of early thymocytes and activated mature T cells. Defective expression of many cell cycle proteins was detected, including cyclin A, cyclin B1, cdc2, cdk2, p27 and the Rb family members p107 and p130 but surprisingly not survivin. Unexpectedly, loss of FoxM1 only affects a few cell cycle proteins in CD4(+)CD8(+) thymocytes and has little effect on their sensitivity to apoptosis and the subsequent steps of T cell differentiation. Thus, regulation of cell cycle genes by FoxM1 is stage- and context-dependent. Public Library of Science 2010-02-16 /pmc/articles/PMC2821927/ /pubmed/20169079 http://dx.doi.org/10.1371/journal.pone.0009229 Text en Xue et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Xue, Ling
Chiang, Leslie
He, Bo
Zhao, You-Yang
Winoto, Astar
FoxM1, a Forkhead Transcription Factor Is a Master Cell Cycle Regulator for Mouse Mature T Cells but Not Double Positive Thymocytes
title FoxM1, a Forkhead Transcription Factor Is a Master Cell Cycle Regulator for Mouse Mature T Cells but Not Double Positive Thymocytes
title_full FoxM1, a Forkhead Transcription Factor Is a Master Cell Cycle Regulator for Mouse Mature T Cells but Not Double Positive Thymocytes
title_fullStr FoxM1, a Forkhead Transcription Factor Is a Master Cell Cycle Regulator for Mouse Mature T Cells but Not Double Positive Thymocytes
title_full_unstemmed FoxM1, a Forkhead Transcription Factor Is a Master Cell Cycle Regulator for Mouse Mature T Cells but Not Double Positive Thymocytes
title_short FoxM1, a Forkhead Transcription Factor Is a Master Cell Cycle Regulator for Mouse Mature T Cells but Not Double Positive Thymocytes
title_sort foxm1, a forkhead transcription factor is a master cell cycle regulator for mouse mature t cells but not double positive thymocytes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2821927/
https://www.ncbi.nlm.nih.gov/pubmed/20169079
http://dx.doi.org/10.1371/journal.pone.0009229
work_keys_str_mv AT xueling foxm1aforkheadtranscriptionfactorisamastercellcycleregulatorformousematuretcellsbutnotdoublepositivethymocytes
AT chiangleslie foxm1aforkheadtranscriptionfactorisamastercellcycleregulatorformousematuretcellsbutnotdoublepositivethymocytes
AT hebo foxm1aforkheadtranscriptionfactorisamastercellcycleregulatorformousematuretcellsbutnotdoublepositivethymocytes
AT zhaoyouyang foxm1aforkheadtranscriptionfactorisamastercellcycleregulatorformousematuretcellsbutnotdoublepositivethymocytes
AT winotoastar foxm1aforkheadtranscriptionfactorisamastercellcycleregulatorformousematuretcellsbutnotdoublepositivethymocytes