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SRCP1 Conveys Resistance to Polyglutamine Aggregation. Mol Cell 2018 07 19;71(2):216-228.e7

Date

07/22/2018

Pubmed ID

30029002

Pubmed Central ID

PMC6091221

DOI

10.1016/j.molcel.2018.07.008

Scopus ID

2-s2.0-85049861465   1 Citation

Abstract

The polyglutamine (polyQ) diseases are a group of nine neurodegenerative diseases caused by the expansion of a polyQ tract that results in protein aggregation. Unlike other model organisms, Dictyostelium discoideum is a proteostatic outlier, naturally encoding long polyQ tracts yet resistant to polyQ aggregation. Here we identify serine-rich chaperone protein 1 (SRCP1) as a molecular chaperone that is necessary and sufficient to suppress polyQ aggregation. SRCP1 inhibits aggregation of polyQ-expanded proteins, allowing for their degradation via the proteasome, where SRCP1 is also degraded. SRCP1's C-terminal domain is essential for its activity in cells, and peptides that mimic this domain suppress polyQ aggregation in vitro. Together our results identify a novel type of molecular chaperone and reveal how nature has dealt with the problem of polyQ aggregation.

Author List

Santarriaga S, Haver HN, Kanack AJ, Fikejs AS, Sison SL, Egner JM, Bostrom JR, Seminary ER, Hill RB, Link BA, Ebert AD, Scaglione KM

Authors

Allison D. Ebert PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
Ronald Blake Hill PhD Professor in the Biochemistry department at Medical College of Wisconsin
Brian A. Link PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Cell Line
Dictyostelium
HEK293 Cells
Humans
Molecular Chaperones
Peptides
Proteasome Endopeptidase Complex
Protein Binding
Serine
Ubiquitin
jenkins-FCD Prod-411 e00897e83867fcfa48419861683711f8d99adb75