Abstract |
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been reported to interact with proteins containing the polyglutamine ( polyQ) domain. The present study was undertaken to evaluate the potential contributions of the polyQ and polyproline ( polyP) domains to the co-localization of mutant huntingtin (htt) and GAPDH. Overexpression of N-terminal htt (1-969 amino acids) with 100Q and 46Q (htt1-969-100Q and httl-969-46Q, mutant htt) in human mammary gland carcinoma MCF-7 cells formed more htt aggregates than that of htt1-969-18Q (wild-type htt). The co-localization of GAPDH with htt aggregates was found in the cells expressing mutant but not wild-type htt. Deletion of the polyP region in the N-terminal htt had no effect on the co-localization of GAPDH and mutant htt aggregates. These results suggest that the polyQ domain, but not the polyP domain, plays a role in the sequestration of GAPDH to aggregates by mutant htt. This effect might contribute to the dysfunction of neurons caused by mutant htt in Huntington's disease.
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Authors | Junchao Wu, Fang Lin, Zhenghong Qin |
Journal | Acta biochimica et biophysica Sinica
(Acta Biochim Biophys Sin (Shanghai))
Vol. 39
Issue 11
Pg. 885-90
(Nov 2007)
ISSN: 1745-7270 [Electronic] China |
PMID | 17989880
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- HTT protein, human
- Huntingtin Protein
- Multiprotein Complexes
- Nerve Tissue Proteins
- Nuclear Proteins
- Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+)
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Topics |
- Breast Neoplasms
(chemistry, genetics, metabolism)
- Cell Line
- Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+)
(chemistry, metabolism)
- Humans
- Huntingtin Protein
- Multiprotein Complexes
(chemistry, genetics, metabolism)
- Mutation
- Nerve Tissue Proteins
(chemistry, genetics, metabolism)
- Nuclear Proteins
(chemistry, genetics, metabolism)
- Structure-Activity Relationship
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