دورية أكاديمية
Regulation of purine metabolism connects KCTD13 to a metabolic disorder with autistic features
| العنوان: | Regulation of purine metabolism connects KCTD13 to a metabolic disorder with autistic features |
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| المؤلفون: | Madison, Jon M., Duong, Karen, Vieux, Ellen F., Udeshi, Namrata D., Iqbal, Sumaiya, Requadt, Elise, Fereshetian, Shaunt, Lewis, Michael C., Gomes, Antonio S., Pierce, Kerry A., Platt, Randall, id_orcid:0 000-0002-2914-7052, Zhang, Feng, Campbell, Arthur J., Lal, Dennis, Wagner, Florence F., Clish, Clary B., Carr, Steven A., Sheng, Morgan, Cottrell, Jeffrey R. |
| المصدر: | iScience, 24 (1) |
| بيانات النشر: | Cell Press |
| سنة النشر: | 2021 |
| المجموعة: | ETH Zürich Research Collection |
| الوصف: | Genetic variation of the 16p11.2 deletion locus containing the KCTD13 gene and of CUL3 is linked with autism. This genetic connection suggested that substrates of a CUL3-KCTD13 ubiquitin ligase may be involved in disease pathogenesis. Comparison of Kctd13 mutant (Kctd13(-/-)) and wild-type neuronal ubiquitylomes identified adenylosuccinate synthetase (ADSS), an enzyme that catalyzes the first step in adenosine monophosphate (AMP) synthesis, as a KCTD13 ligase substrate. In Kctd13(-/-) neurons, there were increased levels of succinyl-adenosine (S-Ado), a metabolite downstream of ADSS. Notably, S-Ado levels are elevated in adenylosuccinate lyase deficiency, a metabolic disorder with autism and epilepsy phenotypes. The increased S-Ado levels in Kctd13(-/-)neurons were decreased by treatment with an ADSS inhibitor. Lastly, functional analysis of human KCTD13 variants suggests that KCTD13 variationmay alter ubiquitination of ADSS. These data suggest that succinyl-AMP metabolites accumulate in Kctd13(-/-) neurons, and this observation may have implications for our understanding of 16p11.2 deletion syndrome. ; ISSN:2589-0042 |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/application/pdf |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/wos/000612996900054; http://hdl.handle.net/20.500.11850/495232Test |
| DOI: | 10.3929/ethz-b-000495232 |
| الإتاحة: | https://doi.org/20.500.11850/495232Test https://doi.org/10.3929/ethz-b-000495232Test https://doi.org/10.1016/j.isci.2020.101935Test https://hdl.handle.net/20.500.11850/495232Test |
| حقوق: | info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0Test/ ; Creative Commons Attribution 4.0 International |
| رقم الانضمام: | edsbas.FCD3E1A4 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3929/ethz-b-000495232 |
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