title: Inhibition of autophagy by TAB2 and TAB3.
abstract: Autophagic responses are coupled to the activation of the inhibitor of NF-κB kinase (IKK). Here, we report that the essential autophagy mediator Beclin 1 and TGFβ-activated kinase 1 (TAK1)-binding proteins 2 and 3 (TAB2 and TAB3), two upstream activators of the TAK1-IKK signalling axis, constitutively interact with each other via their coiled-coil domains (CCDs). Upon autophagy induction, TAB2 and TAB3 dissociate from Beclin 1 and bind TAK1. Moreover, overexpression of TAB2 and TAB3 suppresses, while their depletion triggers, autophagy. The expression of the C-terminal domain of TAB2 or TAB3 or that of the CCD of Beclin 1 competitively disrupts the interaction between endogenous Beclin 1, TAB2 and TAB3, hence stimulating autophagy through a pathway that requires endogenous Beclin 1, TAK1 and IKK to be optimally efficient. These results point to the existence of an autophagy-stimulatory 'switch' whereby TAB2 and TAB3 abandon inhibitory interactions with Beclin 1 to engage in a stimulatory liaison with TAK1.
authors.affiliation: INSERM, U848, Villejuif, France.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Criollo
authors.forename: Mireia
authors.initials: M
authors.lastname: Niso-Santano
authors.forename: Shoaib Ahmad
authors.initials: SA
authors.lastname: Malik
authors.forename: Mickael
authors.initials: M
authors.lastname: Michaud
authors.forename: Eugenia
authors.initials: E
authors.lastname: Morselli
authors.forename: Guillermo
authors.initials: G
authors.lastname: Mariño
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lachkar
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Arkhipenko
authors.forename: Francis
authors.initials: F
authors.lastname: Harper
authors.forename: Gérard
authors.initials: G
authors.lastname: Pierron
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Rain
authors.forename: Jun
authors.initials: J
authors.lastname: Ninomiya-Tsuji
authors.forename: José M
authors.initials: JM
authors.lastname: Fuentes
authors.forename: Sergio
authors.initials: S
authors.lastname: Lavandero
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Galluzzi
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Maiuri
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy; D000071186:Beclin-1; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D020798:Two-Hybrid System Techniques
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C410585:TAB2 protein, human; C481053:TAB3 protein, human
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