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Autosomal dominant diabetes associated with a novel ZYG11A mutation resulting in cell cycle arrest in beta-cells.
Citation | “Autosomal Dominant Diabetes Associated With A Novel Zyg11A Mutation Resulting In Cell Cycle Arrest In Beta-Cells.”. Molecular And Cellular Endocrinology, p. 111126. . |
Center | Joslin Diabetes Center |
Author | Chutima Charoensuk, Prapaporn Jungtrakoon Thamtarana, Chutima Chanprasert, Watip Tangjittipokin, Jun Shirakawa, Yu Togashi, Kazuki Orime, Pucharee Songprakhon, Chartchai Chaichana, Zuroida Abubakar, Paweena Ouying, Jatuporn Sujjitjoon, Alessandro Doria, Nattachet Plengvidhya, Pa-Thai Yenchitsomanus |
Keywords | Cell cycle arrest, Familial diabetes of adulthood, Mutation, ZYG11A |
Abstract |
Diabetes is a genetically heterogeneous disease, for which we are aiming to identify causative genes. Here, we report a missense mutation (c.T1424C:p.L475P) in ZYG11A identified by exome sequencing as segregating with hyperglycemia in a Thai family with autosomal dominant diabetes. ZYG11A functions as a target recruitment subunit of an E3 ubiquitin ligase complex that plays an important role in the regulation of cell cycle. We demonstrate an increase in cells arrested at G/mitotic phase among beta-cells deficient for ZYG11A or overexpressing L475P-ZYG11A, which is associated with a decreased growth rate. This is the first evidence linking a ZYG11A mutation to hyperglycemia, and suggesting ZYG11A as a cell cycle regulator required for beta-cell growth. Since most family members were either overweight or obese, but only mutation carriers developed hyperglycemia, our data also suggests the ZYG11A mutation as a genetic factor predisposing obese individuals to beta-cell failure in maintenance of glucose homeostasis. |
Year of Publication |
2021
|
Journal |
Molecular and cellular endocrinology
|
Volume |
522
|
Number of Pages |
111126
|
Date Published |
12/2021
|
ISSN Number |
1872-8057
|
DOI |
10.1016/j.mce.2020.111126
|
Alternate Journal |
Mol Cell Endocrinol
|
PMID |
33321115
|
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