[摘要]：Autophagic responses are coupled to the activation of the inhibitor of NF-kappa B kinase 9IKK). Here, we report that the essential autophagy mediator Beclin 1 and TGF beta-activated kinase 1 9TAK1)-binding proteins 2 and 3 9TAB2 and TAB3), two upstream activators of the TAK1-IKK signalling axis, constitutively interact with each other via their coiled-coil domains 9CCDs). 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. The EMBO Journal 92011) 30, 4908-4920. doi:10.1038/emboj.2011.413; Published online 11 November 2011
