In:
Journal of Cellular Biochemistry, Wiley, Vol. 117, No. 8 ( 2016-08), p. 1855-1868
Abstract:
Originally described as a TGF‐β‐inducible gene, tsc‐22 (Transforming growth factor‐beta Stimulated Clone 22) encodes a transcriptional regulator affecting biological processes such as cell growth, differentiation, or apoptosis. Along with GILZ (Glucocorticoid‐Induced Leucine Zipper), TSC‐22 belongs to the evolutionary conserved TSC‐22 Domain family. We previously showed that, in T‐lymphocytes, GILZ expression was induced upon IL‐2 withdrawal, delaying apoptosis through down‐regulation of the pro‐apoptotic protein BIM expression. The aim of this work was then to elucidate the respective roles of GILZ and TSC‐22 upon IL‐2 deprivation‐induced apoptosis. We report here that these two highly homologous genes are concomitantly expressed in most human tissues and in primary T‐lymphocytes and that expression of TSC‐22 promotes T‐lymphocytes apoptosis by inhibiting GILZ functions. Indeed, we demonstrated that TSC‐22 expression in the murine lymphoid CTLL‐2 cell line promoted IL‐2 deprivation‐induced apoptosis. BIM expression and caspases‐9 and ‐3 activities were markedly increased in TSC‐22 expressing clones compared to control clones. Analysis of GILZ expression revealed that TSC‐22 prevented the induction of the GILZ protein upon IL‐2 deprivation, by inhibiting gilz mRNA transcription. These results suggested that TSC‐22 could counteract the protective effect of GILZ on IL‐2‐deprivation‐induced apoptosis. Moreover, TSC‐22‐induced inhibition of GILZ expression was also found in CTLL‐2 cells treated with glucocorticoids or TGF‐β. In the human NKL cell line deprived of IL‐2, TSC‐22 showed the same effect and thus may represent a potent repressor of GILZ expression in IL‐2‐dependent cells, independently of the cell type, or the stimulus, leading to an increase of IL‐2‐deprived T‐cells apoptosis. J. Cell. Biochem. 117: 1855–1868, 2016. © 2016 Wiley Periodicals, Inc.
Type of Medium:
Online Resource
ISSN:
0730-2312
,
1097-4644
Language:
English
Publisher:
Wiley
Publication Date:
2016
detail.hit.zdb_id:
1479976-5
SSG:
12
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