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Zfat ‐Deficient CD4 + CD8 + Double‐Positive Thymocytes Are Susceptible to Apoptosis With Deregulated Activation of p38 and JNK
Author(s) -
Ishikura Shuhei,
Ogawa Masahiro,
Doi Keiko,
Matsuzaki Hiroshi,
Iwaihara Yuri,
Tanaka Yoko,
Tsunoda Toshiyuki,
Hideshima Hiromasa,
Okamura Tadashi,
Shirasawa Senji
Publication year - 2015
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24954
Subject(s) - thymocyte , t cell receptor , cd8 , apoptosis , phosphorylation , t cell , double negative , p38 mitogen activated protein kinases , microbiology and biotechnology , biology , stimulation , immune system , zinc finger , receptor , cd3 , chemistry , gene , endocrinology , immunology , protein kinase a , biochemistry , transcription factor
Zfat, which is a nuclear protein harboring an AT‐hook domain and 18‐repeats of C2H2 zinc‐finger motif, is highly expressed in immune‐related tissues, including the thymus and spleen. T cell specific deletion of the Zfat gene by crossing Zfat f/f mice with LckCre mice yields a significant reduction in the number of CD4 + CD8 + double‐positive (DP) thymocytes. However, physiological role for Zfat in T cell development in the thymus remains unknown. Here, we found that Zfat ‐deficient DP thymocytes in Zfat f/f ‐ LckCre mice were susceptible to apoptosis both at an unstimulated state and in response to T cell receptor (TCR)‐stimulation. The phosphorylation levels of p38 and JNK were elevated in Zfat ‐deficient thymocytes at an unstimulated state with an enhanced phosphorylation of ATF2 and with an over‐expression of Gadd45α⋅ On the other hand, the activation of JNK in the Zfat ‐deficient thymocytes, but not p38, was strengthened and prolonged in response to TCR‐stimulation. All these results demonstrate that Zfat critically participates in the development of DP thymocytes through regulating the activities of p38 and JNK. J. Cell. Biochem. 116: 149–157, 2015. © 2014 Wiley Periodicals, Inc.