Premium
Functional properties of the R154X HNF‐4α protein generated by a mutation associated with maturity‐onset diabetes of the young, type 1
Author(s) -
Laine B.,
Eeckhoute J.,
Suaud L.,
Briche I.,
Furuta H.,
Bell G.I.,
Formstecher P.
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01864-0
Subject(s) - maturity onset diabetes of the young , transactivation , mutation , beta (programming language) , mutant , hepatocyte nuclear factor 4 , endocrinology , hepatocyte nuclear factors , medicine , biology , diabetes mellitus , microbiology and biotechnology , chemistry , type 2 diabetes , gene , genetics , gene expression , transcription factor , nuclear receptor , computer science , programming language
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.