caa a22 4500 397573979 CHVBK 20180308164849.0 cr unu---uuuuu 161202e199609 xx s 000 0 eng 10.1093/hmg/5.9.1311 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.9.1311 Spinocerebellar Ataxia Type-1 and Spinobulbar Muscular Atrophy Gene Products Interact with Glyceraldehyde-3-Phosphate Dehydrogenase [Elektronische Daten] [Beena Koshy, Toni Matilla, Eric N. Burright, Diane E. Merry, Kenneth H. Fischbeck, Harry T. Orr, Huda Y. Zoghbi] Spinocerebellar ataxia type1 (SCA1) is one of several neurodegenerative disorders caused by expansions of translated CAG trinucleotide repeats which code for polyglutamine in the respective proteins. Most hypotheses about the molecular defect in these disorders suggest a gain of function, which may involve interactions with other proteins via the expanded polyglutamine tract. In this study we used ataxin-1, the SCA1 gene product, as a bait in the yeast two-hybrid system and identified the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase as an ataxin-1 interacting protein. In addition, the yeast two hybrid data demonstrate that wild type and mutant ataxin-1 form homo and heterodimers. Physical interaction between GAPDH and ataxin-1 was also demonstrated in vitro. To investigate if GAPDH might interact with other glutamine repeat-containing proteins involved in neurodegenerative disorders, we tested its binding to the androgen receptor which is mutated in spinobulbar muscular atrophy. The androgen receptor interacts with GAPDH both in the yeast two-hybrid system and in vitro. The binding of both ataxin-1 and the androgen receptor to GAPDH does not vary with the length of the polyglutamine tract. While provocative, these findings do not address the selective neuronal loss in each of these disorders in light of the wide expression patterns of GAPDH and the respective polyglutamine containing proteins. Nonetheless, such interactions may increase the susceptibility of specific neurons to a variety of insults and initiate degeneration. © 1996 Oxford University Press Koshy Beena Departments of Pediatrics and Molecular and Human Genetics, and Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA aut Matilla Toni Departments of Pediatrics and Molecular and Human Genetics, and Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA aut Burright Eric N. Departments of Laboratory Medicine and Pathology, Biochemistry and Institute of Human Genetics, University of Minnesota, Minneapolis, Minnesota 55455, USA aut Merry Diane E. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA aut Fischbeck Kenneth H. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA aut Orr Harry T. Departments of Laboratory Medicine and Pathology, Biochemistry and Institute of Human Genetics, University of Minnesota, Minneapolis, Minnesota 55455, USA aut Zoghbi Huda Y. Departments of Pediatrics and Molecular and Human Genetics, and Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA aut Human Molecular Genetics Oxford University Press 5/9(1996-09), 1311-1318 0964-6906 5:9<1311 1996 5 hmg https://doi.org/10.1093/hmg/5.9.1311 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.9.1311 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Koshy Beena Departments of Pediatrics and Molecular and Human Genetics, and Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA aut NATIONALLICENCE 700 1- Matilla Toni Departments of Pediatrics and Molecular and Human Genetics, and Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA aut NATIONALLICENCE 700 1- Burright Eric N. Departments of Laboratory Medicine and Pathology, Biochemistry and Institute of Human Genetics, University of Minnesota, Minneapolis, Minnesota 55455, USA aut NATIONALLICENCE 700 1- Merry Diane E. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA aut NATIONALLICENCE 700 1- Fischbeck Kenneth H. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA aut NATIONALLICENCE 700 1- Orr Harry T. Departments of Laboratory Medicine and Pathology, Biochemistry and Institute of Human Genetics, University of Minnesota, Minneapolis, Minnesota 55455, USA aut NATIONALLICENCE 700 1- Zoghbi Huda Y. Departments of Pediatrics and Molecular and Human Genetics, and Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/9(1996-09), 1311-1318 0964-6906 5:9<1311 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford