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dc.contributor.authorZebol, J.en
dc.contributor.authorHewitt, N.en
dc.contributor.authorMoretti, P.en
dc.contributor.authorLynn, H.en
dc.contributor.authorLake, J.en
dc.contributor.authorLi, P.en
dc.contributor.authorVadas, M.en
dc.contributor.authorWattenberg, B.en
dc.contributor.authorPitson, S.en
dc.identifier.citationInternational Journal of Biochemistry & Cell Biology, 2009; 41(4):822-827en
dc.descriptionCopyright © 2008 Elsevieren
dc.description.abstractSphingosine kinase 1 (SK1) catalyses the generation of sphingosine 1-phosphate (S1P), a bioactive phospholipid that influences a diverse range of cellular processes, including proliferation, survival, adhesion, migration, morphogenesis and differentiation. SK1 is controlled by various mechanisms, including transcriptional regulation, and post-translational activation by phosphorylation and protein–protein interactions which can regulate both the activity and localisation of this enzyme. To gain a better understanding of the regulatory mechanisms controlling SK1 activity and function we performed a yeast two-hybrid screen to identify SK1-interacting proteins. Using this approach we identified that SK1 interacts with subunit 7 (η) of cytosolic chaperonin CCT (chaperonin containing t-complex polypeptide, also called TRiC for TCP-1 ring complex), a hexadecameric chaperonin that binds unfolded polypeptides and mediates their folding and release in an ATP-dependent manner. Further analysis of the SK1–CCTη interaction demonstrated that other CCT/TRiC subunits also associated with SK1 in HEK293T cell lysates in an ATP-sensitive manner, suggesting that the intact, functional, multimeric CCT/TRiC complex associated with SK1. Furthermore, pulse-chase studies indicated that CCT/TRiC binds specifically to newly translated SK1. Finally, depletion of functional CCT/TRiC through the use of RNA interference in HeLa cells or temperature sensitive CCT yeast mutants reduced cellular SK1 activity. Thus, combined this data suggests that SK1 is a CCT/TRiC substrate, and that this chaperonin facilitates folding of newly translated SK1 into its mature active form.en
dc.description.statementofresponsibilityJulia R. Zebol, Niamh M. Hewitt, Paul A. B. Moretti, Helen E. Lynn, Julie A. Lake, Peng Li, Mathew A. Vadas, Binks W. Wattenberg and Stuart M. Pitsonen
dc.publisherPergamon-Elsevier Science Ltden
dc.subjectLeukocytes; Hela Cells; Fibroblasts; Humans; Saccharomyces cerevisiae; Sphingosine; Phosphotransferases (Alcohol Group Acceptor); Lysophospholipids; Chaperonins; Two-Hybrid System Techniques; Transfection; Protein Conformation; Protein Folding; Transcriptional Activation; Chaperonin Containing TCP-1en
dc.titleThe CCT/TRiC chaperonin is required for maturation of sphingosine kinase 1en
dc.typeJournal articleen
pubs.library.collectionMedicine publicationsen
dc.identifier.orcidPitson, S. [0000-0002-9527-2740]en
Appears in Collections:Medicine publications

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