Identification and Functional Analysis of the Novel S179R POU1F1 Mutation Associated with Combined Pituitary Hormone Deficiency

• DOI: 10.1210/jc.2005-2289
• Publication Date: 2006-09-13T02:25:13Z
• Authors: Ichiro Miyata; Sophie Vallette-K...; Alexandru Saveanu; Mizuho Takeuchi; Hideki Yoshikawa; Asako Tajima; Katsuyoshi Tojo; Rachel Reynaud; Magali Gueydan; Alain Enjalbert; Naoko Tajima; Yoshikatsu Eto; Thierry Brue
• Keywords: POU domain; Response element; Prolactin cell

The pituitary-specific transcription factor 1 plays a key role in the development and differentiation of three pituitary cell types: somatotrophs, lactotrophs, thyrotrophs. Several mutations human gene (called POU1F1) have been shown to be responsible for phenotype combined hormone deficiency involving GH, prolactin (PRL), TSH.We identified novel homozygous C G mutation exon 4 POU1F1 (S179R) patient with this rare phenotype. We analyzed functional consequences S179R associated single-amino acid change POU-specific domain.Consequences on transcriptional activities by transfection studies alphaT3 cells, DNA binding ability EMSA, structural properties, nuclear accumulation were investigated.The transactivation capacity mutant was markedly decreased GH1, PRL, TSHbeta, genes. Interestingly, abolished interaction PRL promoter coactivator cAMP response element-binding protein-binding protein but not LIM homeodomain 3. displayed normal element keeping crystallographic data, suggesting that might interfere binding.Together previous our study indicates both cofactors like are critical function properties abnormal proteins variously influenced type mutations.