We have updated our privacy policy. If you have any question, contact us at privacy@scicrunch.org. Dismiss and don't show again

Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Polyglutamine domain modulates the TBP-TFIIB interaction: implications for its normal function and neurodegeneration.

Nature neuroscience | Dec 28, 2007

Expansion of the polyglutamine (polyQ) tract in human TATA-box binding protein (TBP) causes the neurodegenerative disease spinocerebellar ataxia 17 (SCA17). It remains unclear how the polyQ tract regulates normal protein function and induces selective neuropathology in SCA17. We generated transgenic mice expressing polyQ-expanded TBP. These mice showed weight loss, progressive neurological symptoms and neurodegeneration before early death. Expanded polyQ tracts reduced TBP dimerization but enhanced the interaction of TBP with the general transcription factor IIB (TFIIB). In SCA17 transgenic mice, the small heat shock protein HSPB1, a potent neuroprotective factor, was downregulated, and TFIIB occupancy of the Hspb1 promoter was decreased. Overexpression of HSPB1 or TFIIB alleviated mutant TBP-induced neuritic defects. These findings implicate the polyQ domain of TBP in transcriptional regulation and provide insight into the molecular pathogenesis of SCA17.

Pubmed ID: 17994014 RIS Download

Mesh terms: Age Factors | Animals | Animals, Newborn | Brain | Cells, Cultured | Chromatin Immunoprecipitation | Disease Models, Animal | Down-Regulation | Gene Expression Regulation | Heat-Shock Proteins | Humans | Mice | Mice, Transgenic | Microscopy, Electron, Transmission | Mutation | Neoplasm Proteins | Neurodegenerative Diseases | Neurons | Polyglutamic Acid | Rats | TATA-Box Binding Protein | Transcription Factor TFIIB | Transfection

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NINDS NIH HHS, Id: R01 NS041669
  • Agency: NINDS NIH HHS, Id: NS045016
  • Agency: NINDS NIH HHS, Id: R01 NS045016
  • Agency: NIA NIH HHS, Id: AG19206
  • Agency: NINDS NIH HHS, Id: NS36232
  • Agency: NIA NIH HHS, Id: R01 AG031153
  • Agency: NINDS NIH HHS, Id: NS41669
  • Agency: NIGMS NIH HHS, Id: T32 GM008490

Mouse Genome Informatics (Data, Gene Annotation)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.