Defective functions of HNF1A variants on BCL2L1 transactivation and beta-cell growth.
Biochem Biophys Res Commun
; 529(3): 826-833, 2020 08 27.
Article
em En
| MEDLINE
| ID: mdl-32684311
Maturity-onset diabetes of the young type 3 (MODY3) is caused by mutations in a gene encoding transcription factor hepatocyte nuclear factor 1-alpha (HNF1A). Although the roles of HNF1A in regulation of hepatic and pancreatic genes to maintain glucose homeostasis were investigated, the functions of HNF1A are not completely elucidated. To better understand the functions of HNF1A, we characterized mutations of HNF1A in Thai MODY3 patients and studied the functions of wild-type HNF1A and variant proteins. We demonstrate for the first time that HNF1A upregulates transactivation of an anti-apoptotic gene BCL2 Like 1 (BCL2L1) and that all the identified HNF1A variants including p.D80V, p.R203C, p.P475L, and p.G554fsX556, reduce this ability. The four HNF1A variants impair HNF1A function in promoting INS-1 cell transition from G1 to S phase of cell cycle, which thereby retard cell growth. This finding indicates the role of HNF1A in beta-cell viability by upregulation of anti-apoptotic gene expression and also reaffirms its role in beta-cell growth through cell cycle control.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ativação Transcricional
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Diabetes Mellitus Tipo 2
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Células Secretoras de Insulina
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Proteína bcl-X
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Fator 1-alfa Nuclear de Hepatócito
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article