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...

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Main Authors: Ling Xue, Leslie Chiang, Bo He, You-Yang Zhao, Astar Winoto
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2010-02-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0009229&type=printable
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author Ling Xue
Leslie Chiang
Bo He
You-Yang Zhao
Astar Winoto
author_facet Ling Xue
Leslie Chiang
Bo He
You-Yang Zhao
Astar Winoto
author_sort Ling Xue
collection DOAJ
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.
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spelling doaj-art-1dd4e84fa0de48b590828151828394d52025-08-20T02:01:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-02-0152e922910.1371/journal.pone.0009229FoxM1, a forkhead transcription factor is a master cell cycle regulator for mouse mature T cells but not double positive thymocytes.Ling XueLeslie ChiangBo HeYou-Yang ZhaoAstar WinotoFoxM1 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0009229&type=printable
spellingShingle Ling Xue
Leslie Chiang
Bo He
You-Yang Zhao
Astar Winoto
FoxM1, a forkhead transcription factor is a master cell cycle regulator for mouse mature T cells but not double positive thymocytes.
PLoS ONE
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
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0009229&type=printable
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AT lesliechiang foxm1aforkheadtranscriptionfactorisamastercellcycleregulatorformousematuretcellsbutnotdoublepositivethymocytes
AT bohe foxm1aforkheadtranscriptionfactorisamastercellcycleregulatorformousematuretcellsbutnotdoublepositivethymocytes
AT youyangzhao foxm1aforkheadtranscriptionfactorisamastercellcycleregulatorformousematuretcellsbutnotdoublepositivethymocytes
AT astarwinoto foxm1aforkheadtranscriptionfactorisamastercellcycleregulatorformousematuretcellsbutnotdoublepositivethymocytes