Related Experiment Video
Updated: May 22, 2026
11:47
Treating SCA1 Mice with Water-Soluble Compounds to Non-Specifically Boost Mitochondrial Function
Published on: January 22, 2017
SCA1-phosphorylation, a regulator of Ataxin-1 function and pathogenesis
1Institute for Translational Neuroscience, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA. orrxx002@umn.edu
Progress in Neurobiology
|April 26, 2012
Summary
Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disease linked to expanded CAG repeats. Research suggests toxicity arises from an exaggerated native function of Ataxin-1, modulated by phosphorylation.
Area of Science:
- Neurodegenerative diseases
- Genetics
- Molecular biology
Background:
- Spinocerebellar ataxia type 1 (SCA1) is a polyglutamine (polyQ) disease caused by unstable trinucleotide CAG repeat expansion.
- Pathogenesis is thought to involve a gain-of-function mechanism, but its exact nature is debated.
Purpose of the Study:
- To investigate the role of Ataxin-1 (ATXN1) native function and its posttranslational modification in SCA1 pathogenesis.
- To explore how polyglutamine expansion influences ATXN1 function and toxicity.
Main Methods:
- Analysis of Ataxin-1 (ATXN1) protein function in the context of polyglutamine expansion.
- Investigating the role of S776 phosphorylation in modulating ATXN1 interactions and toxicity.
Main Results:
- Evidence indicates SCA1 pathology involves a polyglutamine-induced exaggeration of ATXN1's native function.
- Phosphorylation of S776 in ATXN1 regulates its cellular interactions and modulates toxicity.
Conclusions:
- The gain-of-function mechanism in SCA1 appears to stem from an amplified native function of ATXN1.
- Posttranslational modification, specifically S776 phosphorylation, is a key regulator of ATXN1 function and toxicity in SCA1.
Related Concept Videos
01:20The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
01:19Allosteric Proteins-ATCase
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
02:36DNA Damage can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
02:36DNA Damage Can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
01:02Phosphorylation
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
01:22Amplifying Signals via Enzymatic Cascade
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...