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| A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration |
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| Author(s): Lim J, Hao T, Shaw C, Patel AJ, Szabo G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabasi AL, Vidal M, Zoghbi HY |
| Source: CELL Volume: 125 Issue: 4 Pages: 801-814 Published: MAY 19 2006 |
| Times Cited: 161 References: 56 |
| Abstract: Many human inherited neurodegenerative disorders are characterized by loss of balance due to cerebellar Purkinje cell (PC) degeneration. Although the disease-causing mutations have been identified for a number of these disorders, the normal functions of the proteins involved remain, in many cases, unknown. To gain insight into the function of proteins involved in PC degeneration, we developed an interaction network for 54 proteins involved in 23 inherited ataxias and expanded the network by incorporating literature-curated and evolutionarily conserved interactions. We identified 770 mostly novel protein-protein interactions using a stringent yeast two-hybrid screen; of 75 pairs tested, 83% of the interactions were verified in mammalian cells. Many ataxia-causing proteins share interacting partners, a subset of which have been found to modify neurodegeneration in animal models. This interactome thus provides a tool for understanding pathogenic mechanisms common for this class of neuroclegenerative disorders and for identifying candidate genes for inherited ataxias. |
| Document Type: Article |
| Language: English |
| Reprint Address: Zoghbi, HY (reprint author), Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA |
Addresses:
1. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA
2. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA
3. Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA
4. Howard Hughes Med Inst, Coconut Grove, FL 33133 USA
5. Harvard Univ, Sch Med, Ctr Canc Syst Biol, Boston, MA 02115 USA
6. Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA
7. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA
8. Univ Notre Dame, Ctr Complex Network Res, Notre Dame, IN 46556 USA
9. Univ Notre Dame, Dept Phys, Notre Dame, IN 46556 USA |
| Publisher: CELL PRESS, 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: 047NM |
| ISSN: 0092-8674 |
| DOI: 10.1016/j.cell.2006.03.032 |
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