Identities of Sequestered Proteins in Aggregates from Cells with Induced Polyglutamine Expression

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2001 Apr 20

PMID 11309410

Citations 83

Authors

S T Suhr

M. C. Senut

J P Whitelegge

K F Faull

D B Cuizon

F H Gage

Affiliations

Soon will be listed here.

Abstract

Proteins with expanded polyglutamine (polyQ) tracts have been linked to neurodegenerative diseases. One common characteristic of expanded-polyQ expression is the formation of intracellular aggregates (IAs). IAs purified from polyQ-expressing cells were dissociated and studied by protein blot assay and mass spectrometry to determine the identity, condition, and relative level of several proteins sequestered within aggregates. Most of the sequestered proteins comigrated with bands from control extracts, indicating that the sequestered proteins were intact and not irreversibly bound to the polyQ polymer. Among the proteins found sequestered at relatively high levels in purified IAs were ubiquitin, the cell cycle-regulating proteins p53 and mdm-2, HSP70, the global transcriptional regulator Tata-binding protein/TFIID, cytoskeleton proteins actin and 68-kD neurofilament, and proteins of the nuclear pore complex. These data reveal that IAs are highly complex structures with a multiplicity of contributing proteins.

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