CK2 phospho-dependent binding of R2TP complex to TEL2 is essential for mTOR and SMG1 stability.
Mol Cell
; 39(6): 839-50, 2010 Sep 24.
Article
em En
| MEDLINE
| ID: mdl-20864032
ABSTRACT
TEL2 interacts with and is essential for the stability of all phosphatidylinositol 3-kinase-related kinases (PIKKs), but its mechanism of action remains unclear. Here, we show that TEL2 is constitutively phosphorylated on conserved serines 487 and 491 by casein kinase 2 (CK2). Proteomic analyses establish that the CK2 phosphosite of TEL2 confers binding to the R2TP/prefoldin-like complex, which possesses chaperon/prefoldin activities required during protein complex assembly. The PIH1D1 subunit of the R2TP complex binds directly to the CK2 phosphosite of TEL2 in vitro and is required for the TEL2-R2TP/prefoldin-like complex interaction in vivo. Although the CK2 phosphosite mutant of TEL2 retains association with the PIKKs and HSP90 in cells, failure to interact with the R2TP/prefoldin-like complex results in instability of the PIKKs, principally mTOR and SMG1. We propose that TEL2 acts as a scaffold to coordinate the activities of R2TP/prefoldin-like and HSP90 chaperone complexes during the assembly of the PIKKs.
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Base de dados:
MEDLINE
Assunto principal:
Fosfatidilinositol 3-Quinases
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Complexos Multiproteicos
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Caseína Quinase II
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Proteínas Proto-Oncogênicas c-ets
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Serina-Treonina Quinases TOR
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article