SCA1-Phosphorylation, a regulator of Ataxin-1 function and pathogenesis

Research output: Contribution to journalReview article

21 Citations (Scopus)

Abstract

Spinocerebellar ataxia type 1 (SCA1) is one an intriguing set of nine neurodegenerative diseases caused by the expansion of a unstable trinucleotide CAG repeat where the repeat is located within the coding of the affected gene, i.e. the polyglutamine (polyQ) diseases. A gain-of-function mechanism for toxicity in SCA1, like the other polyQ diseases, is thought to have a major role in pathogenesis. Yet, the specific nature of this gain-of-function is a matter of considerable discussion. An issue concerns whether toxicity stems from the native or normal function of the affected protein versus a novel function induced by polyQ expansion. For SCA1 considerable evidence is accumulating that pathology is mediated by a polyQ-induced exaggeration of a native function of the host protein Ataxin-1 (ATXN1) and that phosphorylation of S776 regulates its interaction with other cellular protein and thereby function. In addition, this posttranslational modification modulates toxicity of ATXN1 with an expanded polyglutamine.

Original languageEnglish (US)
Pages (from-to)179-185
Number of pages7
JournalProgress in Neurobiology
Volume99
Issue number3
DOIs
StatePublished - Dec 1 2012

Fingerprint

Spinocerebellar Ataxias
Phosphorylation
Trinucleotide Repeats
Post Translational Protein Processing
Neurodegenerative Diseases
Ataxin-1
polyglutamine
Proteins
Pathology
Genes

Keywords

  • Pathogenesis
  • Phosphorylation
  • Polyglutamine disease
  • SCA1

Cite this

SCA1-Phosphorylation, a regulator of Ataxin-1 function and pathogenesis. / Orr, Harry T.

In: Progress in Neurobiology, Vol. 99, No. 3, 01.12.2012, p. 179-185.

Research output: Contribution to journalReview article

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