title: A novel function of the monomeric CCTε subunit connects the serum response factor pathway to chaperone-mediated actin folding.
abstract: Correct protein folding is fundamental for maintaining protein homeostasis and avoiding the formation of potentially cytotoxic protein aggregates. Although some proteins appear to fold unaided, actin requires assistance from the oligomeric molecular chaperone CCT. Here we report an additional connection between CCT and actin by identifying one of the CCT subunits, CCTε, as a component of the myocardin-related cotranscription factor-A (MRTF-A)/serum response factor (SRF) pathway. The SRF pathway registers changes in G-actin levels, leading to the transcriptional up-regulation of a large number of genes after actin polymerization. These genes encode numerous actin-binding proteins as well as actin. We show that depletion of the CCTε subunit by siRNA enhances SRF signaling in cultured mammalian cells by an actin assembly-independent mechanism. Overexpression of CCTε in its monomeric form revealed that CCTε binds via its substrate-binding domain to the C-terminal region of MRTF-A and that CCTε is able to alter the nuclear accumulation of MRTF-A after stimulation by serum addition. Given that the levels of monomeric CCTε conversely reflect the levels of CCT oligomer, our results suggest that CCTε provides a connection between the actin-folding capacity of the cell and actin expression.
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, 40530 Gothenburg, Sweden.
authors.forename: Kerryn L
authors.initials: KL
authors.lastname: Elliott
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, 40530 Gothenburg, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Svanström
authors.affiliation: Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University, 10691 Stockholm, Sweden.
authors.forename: Matthias
authors.initials: M
authors.lastname: Spiess
authors.affiliation: Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University, 10691 Stockholm, Sweden.
authors.forename: Roger
authors.initials: R
authors.lastname: Karlsson
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, 40530 Gothenburg, Sweden julie.grantham@cmb.gu.se.
authors.forename: Julie
authors.initials: J
authors.lastname: Grantham
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D041702:BALB 3T3 Cells; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D056404:Chaperonin Containing TCP-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D017510:Protein Folding; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D026362:Serum Response Factor / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D000199:Actins; C431575:MRTFA protein, human; D008840:Microfilament Proteins; D018832:Molecular Chaperones; D034741:RNA, Small Interfering; D026362:Serum Response Factor; D015534:Trans-Activators; D056404:Chaperonin Containing TCP-1