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CK2 Phospho-Dependent Binding of R2TP Complex to TEL2 Is Essential for mTOR and SMG1 Stability
- Source :
- Molecular Cell. 39(6):839-850
- Publication Year :
- 2010
- Publisher :
- Elsevier BV, 2010.
-
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.
- Subjects :
- Cytoplasm
Protein subunit
Telomere-Binding Proteins
Cell Cycle Proteins
Plasma protein binding
Ataxia Telangiectasia Mutated Proteins
Protein complex assembly
Biology
Protein Serine-Threonine Kinases
Models, Biological
Cell Line
Mice
Phosphatidylinositol 3-Kinases
Enzyme Stability
Serine
Animals
Humans
HSP90 Heat-Shock Proteins
Phosphorylation
Casein Kinase II
Molecular Biology
R2TP complex
Binding Sites
Proto-Oncogene Proteins c-ets
TOR Serine-Threonine Kinases
Tumor Suppressor Proteins
DNA Helicases
Cell Biology
Recombinant Proteins
Cell biology
Prefoldin
DNA-Binding Proteins
Biochemistry
Chaperone (protein)
Multiprotein Complexes
biology.protein
ATPases Associated with Diverse Cellular Activities
Casein kinase 2
Apoptosis Regulatory Proteins
Carrier Proteins
Molecular Chaperones
Protein Binding
Subjects
Details
- ISSN :
- 10972765
- Volume :
- 39
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Molecular Cell
- Accession number :
- edsair.doi.dedup.....1d6ed370aced83870adb13a230b6ad3b
- Full Text :
- https://doi.org/10.1016/j.molcel.2010.08.037