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Related Experiment Video

Updated: May 24, 2026

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species

Published on: February 27, 2018

Huntingtin with an expanded polyglutamine repeat affects the Jab1-p27(Kip1) pathway.

S Y Cong¹, B A Pepers, T T Zhou

¹Department of Neurology, Shengjing Hospital of China Medical University, Sanhao Street 36, Shenyang 110003, China. congshuyan@hotmail.com

Neurobiology of Disease

|March 20, 2012

Summary

Researchers identified Jun activation domain-binding protein 1 (Jab1) as a novel target in polyglutamine disorders like Huntington's disease (HD). Mutant huntingtin disrupts Jab1, leading to p27(Kip1) accumulation, impacting disease progression and potentially cancer risk.

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Last Updated: May 24, 2026

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species

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Published on: February 27, 2018

Efficient and Scalable Production of Full-length Human Huntingtin Variants in Mammalian Cells using a Transient Expression System

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Published on: December 10, 2021

Generation of Native, Untagged Huntingtin Exon1 Monomer and Fibrils Using a SUMO Fusion Strategy

Generation of Native, Untagged Huntingtin Exon1 Monomer and Fibrils Using a SUMO Fusion Strategy

Published on: June 27, 2018

Area of Science:

Neurodegenerative Diseases
Molecular Pathogenesis
Genetics

Background:

Polyglutamine repeat expansions cause inherited neurodegenerative disorders, including Huntington's disease (HD).
Transcriptional coactivator CBP deregulation by expanded huntingtin (htt) is implicated in HD pathogenesis.

Purpose of the Study:

To identify novel targets of expanded polyglutamine stretches in neurodegenerative disease.
To investigate the role of Jun activation domain-binding protein 1 (Jab1) in Huntington's disease.

Main Methods:

Co-expression studies of expanded polyglutamine or mutant htt with Jab1.
Analysis of Jab1 aggregation, coactivator function, and p27(Kip1) levels in cell models and HD patient brains.

Main Results:

Jab1 accumulates in aggregates and its coactivator function is suppressed by expanded polyglutamine and mutant htt.
Endogenous Jab1 is recruited into aggregates in an HD cell model, leading to p27(Kip1) accumulation.
p27(Kip1) accumulation is observed in HD patient brains.

Conclusions:

Jab1 is a novel target in polyglutamine disorders, with its repression by mutant htt contributing to molecular pathogenesis.
Interference with the Jab1-p27(Kip1) pathway may influence transcriptional effects and cancer incidence in HD patients.
Findings offer insights into the general molecular pathogenesis of polyglutamine disorders.