Artículos de revistas
Inhibition of autophagy by TAB2 and TAB3
Fecha
2011Registro en:
EMBO Journal, Volumen 30, Issue 24, 2018, Pages 4908-4920
02614189
14602075
10.1038/emboj.2011.413
Autor
Criollo Céspedes, Alfredo
Niso-Santano, Mireia
Malik, Shoaib Ahmad
Michaud, Mickael
Morselli, Eugenia
Mariño, Guillermo
Lachkar, Sylvie
Arkhipenko, Alexander V.
Harper, Francis
Pierron, Gérard
Rain, Jean Christophe
Ninomiya-Tsuji, Jun
Fuentes, José M.
Lavandero González, Sergio
Institución
Resumen
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 Becln 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