p65/RelA Modulates BECN1 Transcription and Autophagy

被引:217
作者
Copetti, Tamara [1 ]
Bertoli, Cosetta [1 ]
Dalla, Emiliano [1 ]
Demarchi, Francesca [1 ]
Schneider, Claudio [1 ,2 ]
机构
[1] Lab Nazl Consorzio Interuniv Biotecnol, I-34012 Trieste, Italy
[2] Univ Udine, Dipartimento Sci & Tecnol Biomed, I-33100 Udine, Italy
关键词
NF-KAPPA-B; NECROSIS-FACTOR-ALPHA; INDUCED CELL-DEATH; BREAST-CANCER CELLS; PROTEIN-KINASE; T-CELLS; INDUCED APOPTOSIS; IMMUNE-RESPONSE; ACTIVATION; SURVIVAL;
D O I
10.1128/MCB.01396-08
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Recently, autophagy has emerged as a critical process in the control of T-cell homeostasis. Given the pivotal role of NF-kappa B in the signaling events of T cells, we have analyzed and unveiled a conserved NF-kappa B binding site in the promoter of the murine and human BECN1 autophagic gene (Atg6). Accordingly, we demonstrate that the NF-kappa B family member p65/RelA upregulates BECN1 mRNA and protein levels in different cellular systems. Moreover, p65-mediated upregulation of BECN1 is coupled to increased autophagy. The newly identified kappa B site in the BECN1 promoter specifically interacts with p65 both in vitro and in living Jurkat cells upon phorbol myristate acetate (PMA)-ionomycin stimulation, where p65 induction is coupled to BECN1 upregulation and autophagy induction. Finally, anti-CD3- and PMA-ionomycin-mediated activation of T-cell receptor signaling in peripheral T cells from lymph nodes of healthy mice results in an upregulation of BECN1 expression that can be blocked by the NF-kappa B inhibitor BAY 11-7082. Altogether, these data suggest that autophagy could represent a novel route modulated by p65 to regulate cell survival and control T-cell homeostasis.
引用
收藏
页码:2594 / 2608
页数:15
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