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Inhibition of autophagy by TAB2 and TAB3
Author(s) -
Criollo Alfredo,
NisoSantano Mireia,
Malik Shoaib Ahmad,
Michaud Mickael,
Morselli Eugenia,
Mariño Guillermo,
Lachkar Sylvie,
Arkhipenko Alexander V,
Harper Francis,
Pierron Gérard,
Rain JeanChristophe,
NinomiyaTsuji Jun,
Fuentes José M,
Lavandero Sergio,
Galluzzi Lorenzo,
Maiuri Maria Chiara,
Kroemer Guido
Publication year - 2011
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2011.413
Subject(s) - biology , autophagy , genetics , computational biology , apoptosis
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.