Pfäffle R W, DiMattia G E, Parks J S, Brown M R, Wit J M, Jansen M, Van der Nat H, Van den Brande J L, Rosenfeld M G, Ingraham H A
Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322.
Science. 1992 Aug 21;257(5073):1118-21. doi: 10.1126/science.257.5073.1118.
A point mutation in the POU-specific portion of the human gene that encodes the tissue-specific POU-domain transcription factor, Pit-1, results in hypopituitarism, with deficiencies of growth hormone, prolactin, and thyroid-stimulating hormone. In two unrelated Dutch families, a mutation in Pit-1 that altered an alanine in the first putative alpha helix of the POU-specific domain to proline was observed. This mutation generated a protein capable of binding to DNA response elements but unable to effectively activate its known target genes, growth hormone and prolactin. The phenotype of the affected individuals suggests that the mutant Pit-1 protein is competent to initiate other programs of gene activation required for normal proliferation of somatotrope, lactotrope, and thyrotrope cell types. Thus, a mutation in the POU-specific domain of Pit-1 has a selective effect on a subset of Pit-1 target genes.
人类基因中编码组织特异性POU结构域转录因子Pit-1的POU特异性部分发生点突变，会导致垂体功能减退，伴有生长激素、催乳素和促甲状腺激素缺乏。在两个不相关的荷兰家族中，观察到Pit-1发生突变，该突变将POU特异性结构域第一个假定的α螺旋中的丙氨酸改变为脯氨酸。这种突变产生了一种能够与DNA反应元件结合但无法有效激活其已知靶基因（生长激素和催乳素）的蛋白质。受影响个体的表型表明，突变的Pit-1蛋白能够启动生长激素细胞、催乳激素细胞和促甲状腺激素细胞类型正常增殖所需的其他基因激活程序。因此，Pit-1的POU特异性结构域中的突变对Pit-1靶基因的一个子集具有选择性作用。
