The Hsp90 cochaperone TTT promotes cotranslational maturation of PIKKs prior to complex assembly
Summary: Phosphatidylinositol 3-kinase-related kinases (PIKKs) are a family of kinases that control fundamental processes, including cell growth, DNA damage repair, and gene expression. Although their regulation and activities are well characterized, little is known about how PIKKs fold and assemble...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-10-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124721013346 |
| _version_ | 1818578481648238592 |
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| author | Damien Toullec Alberto Elías-Villalobos Céline Faux Ambre Noly Gwendaline Lledo Martial Séveno Dominique Helmlinger |
| author_facet | Damien Toullec Alberto Elías-Villalobos Céline Faux Ambre Noly Gwendaline Lledo Martial Séveno Dominique Helmlinger |
| author_sort | Damien Toullec |
| collection | DOAJ |
| description | Summary: Phosphatidylinositol 3-kinase-related kinases (PIKKs) are a family of kinases that control fundamental processes, including cell growth, DNA damage repair, and gene expression. Although their regulation and activities are well characterized, little is known about how PIKKs fold and assemble into active complexes. Previous work has identified a heat shock protein 90 (Hsp90) cochaperone, the TTT complex, that specifically stabilizes PIKKs. Here, we describe a mechanism by which TTT promotes their de novo maturation in fission yeast. We show that TTT recognizes newly synthesized PIKKs during translation. Although PIKKs form multimeric complexes, we find that they do not engage in cotranslational assembly with their partners. Rather, our findings suggest a model by which TTT protects nascent PIKK polypeptides from misfolding and degradation because PIKKs acquire their native state after translation is terminated. Thus, PIKK maturation and assembly are temporally segregated, suggesting that the biogenesis of large complexes requires both dedicated chaperones and cotranslational interactions between subunits. |
| first_indexed | 2024-12-16T06:46:30Z |
| format | Article |
| id | doaj.art-4e940ddd3a524b149fabe48419968f82 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-16T06:46:30Z |
| publishDate | 2021-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-4e940ddd3a524b149fabe48419968f822022-12-21T22:40:32ZengElsevierCell Reports2211-12472021-10-01373109867The Hsp90 cochaperone TTT promotes cotranslational maturation of PIKKs prior to complex assemblyDamien Toullec0Alberto Elías-Villalobos1Céline Faux2Ambre Noly3Gwendaline Lledo4Martial Séveno5Dominique Helmlinger6CRBM, University of Montpellier, CNRS, Montpellier, FranceCRBM, University of Montpellier, CNRS, Montpellier, FranceCRBM, University of Montpellier, CNRS, Montpellier, FranceCRBM, University of Montpellier, CNRS, Montpellier, FranceCRBM, University of Montpellier, CNRS, Montpellier, FranceBioCampus Montpellier, University of Montpellier, CNRS, INSERM, Montpellier, FranceCRBM, University of Montpellier, CNRS, Montpellier, France; Corresponding authorSummary: Phosphatidylinositol 3-kinase-related kinases (PIKKs) are a family of kinases that control fundamental processes, including cell growth, DNA damage repair, and gene expression. Although their regulation and activities are well characterized, little is known about how PIKKs fold and assemble into active complexes. Previous work has identified a heat shock protein 90 (Hsp90) cochaperone, the TTT complex, that specifically stabilizes PIKKs. Here, we describe a mechanism by which TTT promotes their de novo maturation in fission yeast. We show that TTT recognizes newly synthesized PIKKs during translation. Although PIKKs form multimeric complexes, we find that they do not engage in cotranslational assembly with their partners. Rather, our findings suggest a model by which TTT protects nascent PIKK polypeptides from misfolding and degradation because PIKKs acquire their native state after translation is terminated. Thus, PIKK maturation and assembly are temporally segregated, suggesting that the biogenesis of large complexes requires both dedicated chaperones and cotranslational interactions between subunits.http://www.sciencedirect.com/science/article/pii/S2211124721013346PIKKsmultimeric complexchaperonetranslationTTTHSP90 |
| spellingShingle | Damien Toullec Alberto Elías-Villalobos Céline Faux Ambre Noly Gwendaline Lledo Martial Séveno Dominique Helmlinger The Hsp90 cochaperone TTT promotes cotranslational maturation of PIKKs prior to complex assembly Cell Reports PIKKs multimeric complex chaperone translation TTT HSP90 |
| title | The Hsp90 cochaperone TTT promotes cotranslational maturation of PIKKs prior to complex assembly |
| title_full | The Hsp90 cochaperone TTT promotes cotranslational maturation of PIKKs prior to complex assembly |
| title_fullStr | The Hsp90 cochaperone TTT promotes cotranslational maturation of PIKKs prior to complex assembly |
| title_full_unstemmed | The Hsp90 cochaperone TTT promotes cotranslational maturation of PIKKs prior to complex assembly |
| title_short | The Hsp90 cochaperone TTT promotes cotranslational maturation of PIKKs prior to complex assembly |
| title_sort | hsp90 cochaperone ttt promotes cotranslational maturation of pikks prior to complex assembly |
| topic | PIKKs multimeric complex chaperone translation TTT HSP90 |
| url | http://www.sciencedirect.com/science/article/pii/S2211124721013346 |
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