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GLCCI1 is a novel protector against glucocorticoid‐induced apoptosis in T cells
Author(s) -
Kiuchi Zentaro,
Nishibori Yukino,
Kutsuna Satoru,
Kotani Masashi,
Hada Ichiro,
Kimura Toru,
Fukutomi Toshiyuki,
Fukuhara Daisuke,
Ito-Nitta Noriko,
Kudo Akihiko,
Takata Takanobu,
Ishigaki Yasuhito,
Tomosugi Naohisa,
Tanaka Hirotoshi,
Matsushima Satsuki,
Ogasawara Shinya,
Hirayama Yoshiaki,
Takematsu Hiromu,
Yan Kunimasa
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201800344rr
Subject(s) - apoptosis , thymocyte , microbiology and biotechnology , biology , kinase , glucocorticoid receptor , programmed cell death , transfection , phosphorylation , t cell , cell culture , glucocorticoid , immunology , biochemistry , immune system , genetics
Glucocorticoids (GCs) potently induce T‐cell apoptosis in a GC receptor (GR)‐dependent manner and are used to control lymphocyte function in clinical practice. However, its downstream pathways remain controversial. Here, we showed that GC‐induced transcript 1 (GLCCI1) is a novel downstream molecule of the GC‐GR cascade that acts as an antiapoptotic mediator in thymic T cells. GLCCI1 was highly phosphorylated and colocalized with microtubules in GLCCI1‐transfected human embryonic kidney QBI293A cells. GR‐dependent up‐regulation of GLCCI1 was associated with GC‐induced proapoptotic events in a cultured thymocyte cell line. However, GLCCI1 knockdown in a thymocyte cell line led to apoptosis. Consistently, transgenic mice overexpressing human GLCCI1 displayed enlarged thymi that consisted of larger numbers of thymocytes. Further molecular characterization showed that GLCCI1 bound to both dynein light chain LC8‐type 1 (LC8) and its functional kinase, p21‐protein activated kinase 1 (PAK1), thereby inhibiting the kinase activity of PAK1 toward LC8 phosphorylation, a crucial event in apoptotic signaling. GLCCI1 induction facilitated LC8 dimer formation and reduced Bim expression. Thus, GLCCI1 is a candidate factor involved in apoptosis regulation of thymic T cells.—Kiuchi, Z., Nishibori, Y., Kutsuna, S., Kotani, M., Hada, I., Kimura, T., Fukutomi, T., Fukuhara, D., Ito‐Nitta, N., Kudo, A., Takata, T., Ishigaki, Y., Tomosugi, N., Tanaka, H., Matsushima, S., Ogasawara, S., Hirayama, Y., Takematsu, H., Yan, K. GLCCI1 is a novel protector against glucocorticoid‐induced apoptosis in T cells. FASEB J. 33, 7387–7402 (2019). www.fasebj.org