title: Interaction of p53 with the CCT complex promotes protein folding and wild-type p53 activity.
abstract: p53 is a transcription factor that mediates tumor suppressor responses. Correct folding of the p53 protein is essential for these activities, and point mutations that induce conformational instability of p53 are frequently found in cancers. These mutant p53s not only lose wild-type activity but can also acquire the ability to promote invasion and metastasis. We show that folding of wild-type p53 is promoted by an interaction with the chaperonin CCT. Depletion of this chaperone in cells results in the accumulation of misfolded p53, leading to a reduction in p53-dependent gene expression. Intriguingly, p53 proteins mutated to prevent the interaction with CCT show conformational instability and acquire an ability to promote invasion and random motility that is similar to the activity of tumor-derived p53 mutants. Our data therefore suggest that both growth suppression and cell invasion may be differentially regulated functions of wild-type p53.
authors.affiliation: CR-UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
authors.forename: Antonio Garcia
authors.initials: AG
authors.lastname: Trinidad
authors.forename: Patricia A J
authors.initials: PA
authors.lastname: Muller
authors.forename: Jorge
authors.initials: J
authors.lastname: Cuellar
authors.forename: Marta
authors.initials: M
authors.lastname: Klejnot
authors.forename: Max
authors.initials: M
authors.lastname: Nobis
authors.forename: José María
authors.initials: JM
authors.lastname: Valpuesta
authors.forename: Karen H
authors.initials: KH
authors.lastname: Vousden
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D017930:Genes, Reporter; D056385:Group II Chaperonins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D049409:Luciferases, Firefly / Q000096:biosynthesis / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D055550:Protein Stability; D020836:Protein Structure, Quaternary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D021122:Protein Subunits; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D049409:Luciferases, Firefly; D056385:Group II Chaperonins