P57 regulates T-cell development and prevents lymphomagenesis by balancing p53 activity and pre-TCR signaling

Research output: Contribution to journalArticle

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Abstract

T cells are key components of the immune system, playing a central role in cell-mediated immunity. The sequential differentiation of T cells is associated with strict regulation of the cell cycle at each developmental stage. A balance between p53 activity and pre-T cell receptor (TCR) signaling regulates proliferation and differentiation decisions made by these cells. The relation between maintenance of this balance and the function of cell cycle regulators has remained largely unknown, however. We now show that mice with T cell-specific deficiency of the cyclin-dependent kinase inhibitor p57 manifest a differentiation block at the early stage of T cell maturation. Further genetic analysis showed that this defect is attributable to an imbalance betweenp53 activity and pre-TCR signaling caused by hyper activation of the E2F-p53 pathway. Moreover, ablation of both p57 and p53 in T cells led to the development of aggressive thymic lymphomas with a reduced latency compared with that apparent for p53-deficient mice, whereas ablation of p57 alone did not confer susceptibility to this he matologic malignancy. Our results thus show that the p57-E2F-p53 axis plays a pivotal role in the proper development of T cells as well as in the prevention of lymphomagenesis.

Original languageEnglish
Pages (from-to)3429-3439
Number of pages11
JournalBlood
Volume123
Issue number22
DOIs
Publication statusPublished - May 29 2014

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T-cells
T-Cell Antigen Receptor
T-Lymphocytes
Ablation
Cyclin-Dependent Kinase Inhibitor p57
Cell Cycle
Cells
Immune system
Cellular Structures
Cellular Immunity
Immune System
Lymphoma
Chemical activation
Maintenance
Defects
Neoplasms

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

P57 regulates T-cell development and prevents lymphomagenesis by balancing p53 activity and pre-TCR signaling. / Matsumoto, Akinobu; Takeishi, Shoichiro; Nakayama, Keiichi I.

In: Blood, Vol. 123, No. 22, 29.05.2014, p. 3429-3439.

Research output: Contribution to journalArticle

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