FoxM1, a forkhead transcription factor is a master cell cycle regulator for mouse mature T cells but not double positive thymocytes

PLoS One. 2010 Feb 16;5(2):e9229. doi: 10.1371/journal.pone.0009229.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Apoptosis / physiology
  • Blotting, Western
  • CD4 Antigens / metabolism
  • CD8 Antigens / metabolism
  • Cell Cycle / genetics
  • Cell Cycle / physiology*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Proliferation
  • Cyclin B1 / genetics
  • Cyclin B1 / metabolism
  • Female
  • Flow Cytometry
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors / deficiency
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / physiology*
  • Inhibitor of Apoptosis Proteins / genetics
  • Inhibitor of Apoptosis Proteins / metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survivin
  • T-Lymphocytes / cytology
  • T-Lymphocytes / metabolism*
  • Thymus Gland / cytology
  • Thymus Gland / metabolism*

Substances

  • Birc5 protein, mouse
  • CD4 Antigens
  • CD8 Antigens
  • Cell Cycle Proteins
  • Cyclin B1
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors
  • Foxm1 protein, mouse
  • Inhibitor of Apoptosis Proteins
  • Repressor Proteins
  • Survivin