Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/50630
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | The CCT/TRiC chaperonin is required for maturation of sphingosine kinase 1 |
Author: | Zebol, J. Hewitt, N. Moretti, P. Lynn, H. Lake, J. Li, P. Vadas, M. Wattenberg, B. Pitson, S. |
Citation: | The International Journal of Biochemistry and Cell Biology, 2009; 41(4):822-827 |
Publisher: | Pergamon-Elsevier Science Ltd |
Issue Date: | 2009 |
ISSN: | 1357-2725 1878-5875 |
Statement of Responsibility: | Julia 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. Pitson |
Abstract: | Sphingosine 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. |
Keywords: | Leukocytes 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-1 |
Description: | Copyright © 2008 Elsevier |
DOI: | 10.1016/j.biocel.2008.08.012 |
Description (link): | http://www.elsevier.com/wps/find/journaldescription.cws_home/395/description#description |
Published version: | http://dx.doi.org/10.1016/j.biocel.2008.08.012 |
Appears in Collections: | Aurora harvest 5 Medicine publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.