Inhibition of autophagy by TAB2 and TAB3 Academic Article uri icon


MeSH Major

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • Autophagy
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins


  • 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.

publication date

  • December 14, 2011



  • Academic Article



  • eng

PubMed Central ID

  • PMC3243630

Digital Object Identifier (DOI)

  • 10.1038/emboj.2011.413

PubMed ID

  • 22081109

Additional Document Info

start page

  • 4908

end page

  • 20


  • 30


  • 24