title: The anti-apoptotic Bcl-B protein inhibits BECN1-dependent autophagic cell death.
abstract: Bcl-2 family members are key modulators of apoptosis that have recently been shown to also regulate autophagy. It has been previously reported that Bcl-2 and Bcl-X(L) bind and inhibit BECN1, an essential mediator of autophagy. Bcl-B is an anti-apoptotic member of the Bcl-2 family that possesses the four BH (Bcl-2 homology) domains (BH1, BH2, BH3 and BH4) and a predicted C-terminal trans-membrane domain. Although the anti-apoptotic properties of Bcl-B are well characterized, its physiological function remains to be established. In the present study, we first established that Bcl-B interacts with the BH3 domain of BECN1. We also showed that Bcl-B overexpression reduces autophagy triggered by a variety of pro-autophagic stimuli. This impairment of autophagy was closely related to the capacity of Bcl-B to bind to BECN1. Importantly, we have demonstrated that Bcl-B knockdown triggers autophagic cell death and sensitizes cells to amino acid starvation. The cell death induced by Bcl-B knockdown was partially dependent on components of the autophagy machinery (LC3; BECN1; ATG5). These findings reveal a new role of Bcl-B in the regulation of autophagy.
authors.affiliation: Faculté de Médecine, Institut Signalisation et Pathologie (IFR 50), Université de Nice Sophia-Antipolis, Nice, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Robert
authors.forename: Cecile
authors.initials: C
authors.lastname: Gastaldi
authors.forename: Alexandre
authors.initials: A
authors.lastname: Puissant
authors.forename: Amine
authors.initials: A
authors.lastname: Hamouda
authors.forename: Arnaud
authors.initials: A
authors.lastname: Jacquel
authors.forename: Maeva
authors.initials: M
authors.lastname: Dufies
authors.forename: Nathalie
authors.initials: N
authors.lastname: Belhacene
authors.forename: Pascal
authors.initials: P
authors.lastname: Colosetti
authors.forename: John C
authors.initials: JC
authors.lastname: Reed
authors.forename: Patrick
authors.initials: P
authors.lastname: Auberger
authors.forename: Fréderic
authors.initials: F
authors.lastname: Luciano
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000172:deficiency; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001343:Autophagy; D000071186:Beclin-1; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D051017:Apoptosis Regulatory Proteins; C117144:BCL2-like 10 protein; C491997:BECN1 protein, human; D000071186:Beclin-1; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D019253:Proto-Oncogene Proteins c-bcl-2