Functional properties of the R154X HNF‐4α protein generated by a mutation associated with maturity‐onset diabetes of the young, type 1
- 7 August 2000
- journal article
- Published by Wiley in FEBS Letters
- Vol. 479 (1-2) , 41-45
- https://doi.org/10.1016/s0014-5793(00)01864-0
Abstract
Mutations in the hepatocyte nuclear factor 4α (HNF-4α) gene are associated with one form of maturity-onset diabetes of the young (MODY1). The R154X mutation generates a protein lacking the E-domain which is required for normal HNF-4α functions. Since pancreatic β-cell dysfunction is a feature of MODY1 patients, we compared the functional properties of the R154X mutant in insulin-secreting pancreatic β-cells and non-β-cells. The R154X mutation did not affect nuclear localisation in β-cells and non-β-cells. However, it did lead to a greater impairment of HNF-4α function in β-cells compared to non-β-cells, including a complete loss of transactivation activity and a dominant-negative behaviour.Keywords
This publication has 30 references indexed in Scilit:
- A missense mutation in hepatocyte nuclear factor-4 alpha, resulting in a reduced transactivation activity, in human late-onset non-insulin-dependent diabetes mellitus.Journal of Clinical Investigation, 1998
- Functional Association between CBP and HNF4 inTrans-activationBiochemical and Biophysical Research Communications, 1997
- Hepatic function in a family with a nonsense mutation (R154X) in the hepatocyte nuclear factor-4alpha/MODY1 gene.Journal of Clinical Investigation, 1997
- Functional Domains of the Nuclear Receptor Hepatocyte Nuclear Factor 4Published by Elsevier ,1997
- Distal Apolipoprotein C-III Regulatory Elements F to J Act as a General Modular Enhancer for Proximal Promoters That Contain Hormone Response ElementsArteriosclerosis, Thrombosis, and Vascular Biology, 1997
- Mutations in the hepatocyte nuclear factor-1α gene in maturity-onset diabetes of the young (MODY3)Nature, 1996
- Mutations in the hepatocyte nuclear factor-4α gene in maturity-onset diabetes of the young (MODY1)Nature, 1996
- Transcriptional hierarchy in Xenopus embryogenesis: HNF4 a maternal factor involved in the developmental activation of the gene encoding the tissue specific transcription factor HNF1α (LFB1)Mechanisms of Development, 1996
- Complex Interactions between SP1 Bound to Multiple Distal Regulatory Sites and HNF-4 Bound to the Proximal Promoter Lead to Transcriptional Activation of Liver-Specific Human APOCIII GeneBiochemistry, 1995
- Liver-enriched transcription factor HNF-4 is a novel member of the steroid hormone receptor superfamily.Genes & Development, 1990