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PMID: 19289499 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

p65/RelA modulates BECN1 transcription and autophagy.

Molecular and cellular biology ·Vol. 29 ·No. 10 ·2009-05-00 ·Pages 2594-608

Copetti T, Bertoli C, Dalla E, Demarchi F, Schneider C

Abstract

Recently, autophagy has emerged as a critical process in the control of T-cell homeostasis. Given the pivotal role of NF-kappaB in the signaling events of T cells, we have analyzed and unveiled a conserved NF-kappaB binding site in the promoter of the murine and human BECN1 autophagic gene (Atg6). Accordingly, we demonstrate that the NF-kappaB 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 kappaB 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-kappaB 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.

MeSH Terms
Animals Apoptosis Regulatory Proteins/genetics,metabolism Autophagy/physiology Base Sequence Beclin-1 Cell Line Homeostasis Humans Ionomycin/pharmacology Ionophores/pharmacology Jurkat Cells/physiology Lymphocyte Activation/drug effects Membrane Proteins/genetics,metabolism Mice Molecular Sequence Data NF-kappa B/antagonists & inhibitors,genetics,metabolism Promoter Regions, Genetic Sequence Alignment Signal Transduction/physiology T-Lymphocytes/cytology,drug effects,metabolism Tetradecanoylphorbol Acetate/pharmacology Transcription Factor RelA/genetics,metabolism
Chemicals
Apoptosis Regulatory Proteins BECN1 protein, human Beclin-1 Ionophores Membrane Proteins NF-kappa B Transcription Factor RelA Ionomycin Tetradecanoylphorbol Acetate
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Copetti Tamara
Laboratorio Nazionale Consorzio Interuniversitario Biotecnologie, AREA Science Park, Padriciano 99, 34012 Trieste, Italy.
Bertoli Cosetta
Dalla Emiliano
Demarchi Francesca
Schneider Claudio
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
1098-5549
DOI
10.1128/MCB.01396-08
Published
2009-05-00
Epub
2009-00-16
Pages
2594-608
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC2682036
Subset
IM
Corrections
ErratumIn
PMID: 28754773
External Links
PubMed source DOI: 10.1128/MCB.01396-08 PMC Full Text View journal details
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