p53 contributes to T cell homeostasis through the induction of pro-apoptotic SAP

Harsha S. Madapura, Daniel Salamon, Klas G. Wiman, Sonia Lain, George Klein, Eva Klein, Noémi Nagy

Research output: Article

10 Citations (Scopus)

Abstract

Lack of functional SAP protein, due to gene deletion or mutation, is the cause of X-linked lymphoproliferative disease (XLP), characterized by functionally impaired T and NK cells and a high risk of lymphoma development. We have demonstrated earlier that SAP has a pro-apoptotic function in T and B cells. Deficiency of this function might contribute to the pathogenesis of XLP. We have also shown that SAP is a target of p53 in B cell lines. In the present study, we show that activated primary T cells express p53, which induces SAP expression. p53 is functional as a transcription factor in activated T cells and induces the expression of p21, PUMA and MDM2. PARP cleavage in the late phase of activation indicates that T cells expressing high levels of SAP undergo apoptosis. Modifying p53 levels using Nutlin-3, which specifically dissociates the MDM2-p53 interaction, was sufficient to upregulate SAP expression, indicating that SAP is a target of p53 in T cells. We also demonstrated p53's role as a transcription factor for SAP in activated T cells by ChIP assays. Our result suggests that p53 contributes to T cell homeostasis through the induction of the pro-apoptotic SAP. A high level of SAP is necessary for the activation-induced cell death that is pivotal in termination of the T cell response.

Original languageEnglish
Pages (from-to)4563-4569
Number of pages7
JournalCell Cycle
Volume11
Issue number24
DOIs
Publication statusPublished - dec. 15 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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    Madapura, H. S., Salamon, D., Wiman, K. G., Lain, S., Klein, G., Klein, E., & Nagy, N. (2012). p53 contributes to T cell homeostasis through the induction of pro-apoptotic SAP. Cell Cycle, 11(24), 4563-4569. https://doi.org/10.4161/cc.22810