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Siva-1 negatively regulates NF-κB activity: effect on T-cell receptor-mediated activation-induced cell death (AICD).
- Source :
- Oncogene; 6/8/2006, Vol. 25 Issue 24, p3458-3462, 5p, 4 Diagrams
- Publication Year :
- 2006
-
Abstract
- Ligation of TCRs on stimulated T cells leads to activation-induced cell death (AICD) resulting in the downregulation of immune responses, a process essential for T-cell homeostasis. In this study, using transformed T-cell lines such as Jurkat and Do11.10 as cellular models of TCR-mediated AICD, we have demonstrated that the proapoptotic protein Siva-1 is required for TCR-induced apoptosis. Knockdown of Siva-1 rendered T cells specifically resistant to anti-CD3 but not Fas-induced apoptosis. Further, we observed that in Siva-1 knockout Jurkat cells, TCR-mediated activation of the canonical and non-canonical limbs of the NF-κB pathway are significantly enhanced as reflected by elevated nuclear levels of p65 and RelB, respectively. In addition, loss of endogenous Siva-1 also resulted in the enhanced expression of NF-κB- responsive anti-apoptotic genes such as Bcl-xL and c-FLIP. Interestingly, the c-FLIP<subscript>short</subscript> was detected only in TCR-ligated Siva-1 knockdown Jurkat cells. These results demonstrate a significant role for endogenous Siva-1, through its inhibitory effect on NF-κB activity, in TCR-mediated AICD with implications in peripheral tolerance, T-cell homeostasis and cancer.Oncogene (2006) 25, 3458–3462. doi:10.1038/sj.onc.1209381; published online 20 February 2006 [ABSTRACT FROM AUTHOR]
- Subjects :
- T cells
CELL death
IMMUNE response
HOMEOSTASIS
PROTEINS
APOPTOSIS
GENE expression
Subjects
Details
- Language :
- English
- ISSN :
- 09509232
- Volume :
- 25
- Issue :
- 24
- Database :
- Complementary Index
- Journal :
- Oncogene
- Publication Type :
- Academic Journal
- Accession number :
- 21091157
- Full Text :
- https://doi.org/10.1038/sj.onc.1209381