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Molecular and Cellular Biology, May 2009, p. 2594-2608, Vol. 29, No. 10
0270-7306/09/$08.00+0     doi:10.1128/MCB.01396-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

p65/RelA Modulates BECN1 Transcription and Autophagy{triangledown} ,{dagger}

Tamara Copetti,1 Cosetta Bertoli,1 Emiliano Dalla,1 Francesca Demarchi,1* and Claudio Schneider1,2*

Laboratorio Nazionale Consorzio Interuniversitario Biotecnologie, AREA Science Park, Padriciano 99, 34012 Trieste, Italy,1 Dipartimento di Scienze e Tecnologie Biomediche, Universita’ degli Studi di Udine, p.le Kolbe 4, 33100 Udine, Italy2

Received 5 September 2008/ Returned for modification 20 November 2008/ Accepted 6 March 2009

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.

* Corresponding author. Mailing address: Laboratorio Nazionale Consorzio Interuniversitario Biotecnologie, AREA Science Park, Padriciano 99, 34012 Trieste, Italy. Phone: 39 040 3756804. Fax: 39 040 398990. E-mail for Francesca Demarchi: francesca.demarchi{at}lncib.it. E-mail for Claudio Schneider: schneide{at}lncib.it

{triangledown} Published ahead of print on 16 March 2009.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, May 2009, p. 2594-2608, Vol. 29, No. 10
0270-7306/09/$08.00+0     doi:10.1128/MCB.01396-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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