Phosphorylation Of Ataxin-1

A link between basic research and clinical application in spinocerebellar ataxia type 1

Kerri M. Carlson, Harry T Orr

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Spinocerebellar Ataxia type 1 (SCAl) is an autosomal dominant neurodegenerative disease caused by an expanded polyglutamine tract in ataxin-1. Phosphorylation of ataxin-1 at S776 is an important mediator of ataxin-1 turnover and SCAl pathogenesis. Mice expressing a SCA1 transgene are behaviorally indistinguishable from wild-type mice. Pathologically, these mice develop a very mild SCAl phenotype late in life. On a molecular level, S776 has been shown to mediate the interaction between ataxin-1 and 14-3-3. 14-3-3 binding to ataxin-1 stabilizes the ataxin-1 protein. A cell-based assay can also be used to identify two signaling pathways important for regulating S776 phosphorylation. One pathway appears to work in a calcium-dependent manner to phosphorylate both mutant and wild-type ataxin-1. The second pathway is mutant specific and involves PI3K/AKT signaling. The discovery of S776 phosphorylation is an important regulator of ataxin-1 turnover, as well as the identification of two signaling pathways involved in this regulation opened up a new area to explore for therapeutic development in SCAl.

Original languageEnglish (US)
Title of host publicationGenetic Instabilities and Neurological Diseases, Second Edition
PublisherElsevier Inc.
Pages339-349
Number of pages11
ISBN (Print)9780123694621
DOIs
StatePublished - Dec 1 2006

Fingerprint

Spinocerebellar Ataxias
Phosphorylation
Research
Neurodegenerative diseases
Ataxin-1
Transgenes
Phosphatidylinositol 3-Kinases
Neurodegenerative Diseases
Assays
Calcium
Phenotype

Cite this

Carlson, K. M., & Orr, H. T. (2006). Phosphorylation Of Ataxin-1: A link between basic research and clinical application in spinocerebellar ataxia type 1. In Genetic Instabilities and Neurological Diseases, Second Edition (pp. 339-349). Elsevier Inc.. https://doi.org/10.1016/B978-012369462-1/50023-5

Phosphorylation Of Ataxin-1 : A link between basic research and clinical application in spinocerebellar ataxia type 1. / Carlson, Kerri M.; Orr, Harry T.

Genetic Instabilities and Neurological Diseases, Second Edition. Elsevier Inc., 2006. p. 339-349.

Research output: Chapter in Book/Report/Conference proceedingChapter

Carlson, KM & Orr, HT 2006, Phosphorylation Of Ataxin-1: A link between basic research and clinical application in spinocerebellar ataxia type 1. in Genetic Instabilities and Neurological Diseases, Second Edition. Elsevier Inc., pp. 339-349. https://doi.org/10.1016/B978-012369462-1/50023-5
Carlson, Kerri M. ; Orr, Harry T. / Phosphorylation Of Ataxin-1 : A link between basic research and clinical application in spinocerebellar ataxia type 1. Genetic Instabilities and Neurological Diseases, Second Edition. Elsevier Inc., 2006. pp. 339-349
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