Inhibition of autophagy by TAB2 and TAB3.

نویسندگان

  • Alfredo Criollo
  • Mireia Niso-Santano
  • Shoaib Ahmad Malik
  • Mickael Michaud
  • Eugenia Morselli
  • Guillermo Mariño
  • Sylvie Lachkar
  • Alexander V Arkhipenko
  • Francis Harper
  • Gérard Pierron
  • Jean-Christophe Rain
  • Jun Ninomiya-Tsuji
  • José M Fuentes
  • Sergio Lavandero
  • Lorenzo Galluzzi
  • Maria Chiara Maiuri
  • Guido Kroemer
چکیده

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.

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عنوان ژورنال:
  • The EMBO journal

دوره 30 24  شماره 

صفحات  -

تاریخ انتشار 2011