Yin Yang 1 promotes thymocyte survival by downregulating p53

Liang Chen, Daniel P. Foreman, Derek B. Sant'Angelo, Michael S. Krangel

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Yin Yang 1 (YY1) is a zinc finger protein that functions as a transcriptional activator or repressor and participates in multiple biological processes, including development and tumorigenesis. To investigate the role of YY1 in developing T cells, we used mouse models that depleted YY1 at two distinct stages of thymocyte development. When YY1 was depleted in CD4-CD8- double-negative thymocytes, development to the CD4+CD8+ double-positive stage was impaired, due to increased apoptosis that prevented expansion of post-β-selection thymocytes. When YY1 was depleted in double-positive thymocytes, they underwent increased cellautonomous apoptosis in vitro and displayed a shorter lifespan in vivo, as judged by their ability to undergo secondary Vα-to-Jα recombination. Mechanistically, we found that the increased apoptosis in YY1-deficient thymocytes was attributed to overexpression of p53, because concurrent loss of p53 completely rescued the developmental defects of YY1-deficient thymocytes. These results indicated that YY1 functions as a critical regulator of thymocyte survival and that it does so by suppressing the expression of p53.

Original languageEnglish (US)
Pages (from-to)2572-2582
Number of pages11
JournalJournal of Immunology
Volume196
Issue number6
DOIs
StatePublished - Mar 15 2016

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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