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PLoS Biol. 2014 Apr 22;12(4):e1001844. doi: 10.1371/journal.pbio.1001844. eCollection 2014 Apr.

Modulation of STAT3 folding and function by TRiC/CCT chaperonin.

Author information

1
Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America.
2
Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America.
3
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America.
4
Department of Biology and the BioX Program, Stanford University, Stanford, California, United States of America.
5
Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America; Department of Cellular and Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America.

Abstract

Signal transducer and activator of transcription 3 (Stat3) transduces signals of many peptide hormones from the cell surface to the nucleus and functions as an oncoprotein in many types of cancers, yet little is known about how it achieves its native folded state within the cell. Here we show that Stat3 is a novel substrate of the ring-shaped hetero-oligomeric eukaryotic chaperonin, TRiC/CCT, which contributes to its biosynthesis and activity in vitro and in vivo. TRiC binding to Stat3 was mediated, at least in part, by TRiC subunit CCT3. Stat3 binding to TRiC mapped predominantly to the β-strand rich, DNA-binding domain of Stat3. Notably, enhancing Stat3 binding to TRiC by engineering an additional TRiC-binding domain from the von Hippel-Lindau protein (vTBD), at the N-terminus of Stat3, further increased its affinity for TRiC as well as its function, as determined by Stat3's ability to bind to its phosphotyrosyl-peptide ligand, an interaction critical for Stat3 activation. Thus, Stat3 levels and function are regulated by TRiC and can be modulated by manipulating its interaction with TRiC.

PMID:
24756126
PMCID:
PMC3995649
DOI:
10.1371/journal.pbio.1001844
[Indexed for MEDLINE]
Free PMC Article
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