| First Author | Guan WJ | Year | 2013 |
| Journal | Biochem Biophys Res Commun | Volume | 430 |
| Issue | 2 | Pages | 780-6 |
| PubMed ID | 23206699 | Mgi Jnum | J:193871 |
| Mgi Id | MGI:5469801 | Doi | 10.1016/j.bbrc.2012.11.069 |
| Citation | Guan WJ, et al. (2013) Spinocerebellar ataxia type 35 (SCA35)-associated transglutaminase 6 mutants sensitize cells to apoptosis. Biochem Biophys Res Commun 430(2):780-6 |
| abstractText | Spinocerebellar ataxia type 35 (SCA35) is an autosomal dominant neurodegenerative disorder. In our previous study, using exome sequencing and linkage analysis, two missense mutations of the transglutaminase 6 (TGM6) gene were identified as causative for SCA35. TGM6 encodes transglutaminase 6 (TG6), a member of the transglutaminase family of enzymes that catalyze the formation of a covalent bond between a free amine group and the gamma-carboxamide group of protein- or peptide-bound glutamine. However, the precise role of TG6 in contributing to SCA35 remains unclear. In this study, we analyzed the subcellular distribution, expression and in vitro activity of two missense mutations of TG6 (D327G, L517W) and found that both mutants exhibited decreased transglutaminase activity and stability. Furthermore, overexpressing the TG6 mutants sensitized cells to staurosporine-induced apoptosis by increasing the activity of caspases. We propose that the pro-apoptotic role of these mutants might underlie the pathogenesis of SCA35. |
