Mueller Jonathan W, Bayer Peter
Institute for Structural and Medicinal Biochemistry, Centre for Medical Biotechnology-ZMB, University of Duisburg-Essen, 45117 Essen, Germany.
Perspect Medicin Chem. 2008 Mar 7;2:11-20. doi: 10.4137/pmc.s496.
The parvulin-type peptidyl-prolyl cis/trans isomerase Pin1 is subject of intense biochemical and clinical research as it seems to be involved in the pathogenesis of certain cancers and protein folding illnesses like Alzheimer's and Parkinson's disease. In addition to Pin1, the human genome only contains a single other parvulin locus encoding two protein species-Par14 and Par17. Much less is known about these enzymes although their sequences are highly conserved in all metazoans. Parvulin has been proposed to function as Pin1 complementing enzyme in cell cycle regulation and in chromatin remodelling. Pharmaceutical modulation of Par14 might therefore have benefits for certain types of cancer. Moreover, the Par17 protein that has been shown to be confined to anthropoid primate species only might provide a deeper understanding for human-specific brain development. This review aims at stimulating further research on Par14 and Par17 that are overlooked drug targets in the shadow of an overwhelming plethora of Pin1 literature by summarising all current knowledge on these parvulin proteins.
小脯氨酸异构酶Pin1是一种小脯氨酸型肽基脯氨酰顺/反异构酶，因其似乎参与某些癌症的发病机制以及阿尔茨海默病和帕金森病等蛋白质折叠疾病的发病过程，而成为深入生化和临床研究的对象。除了Pin1，人类基因组中仅包含另一个小脯氨酸基因座，该基因座编码两种蛋白质——Par14和Par17。尽管这些酶的序列在所有后生动物中高度保守，但对它们的了解却少得多。有人提出小脯氨酸异构酶在细胞周期调控和染色质重塑中作为Pin1的补充酶发挥作用。因此，对Par14进行药物调节可能对某些类型的癌症有益。此外，已证明仅存在于类人猿灵长类物种中的Par17蛋白可能有助于更深入地理解人类特有的大脑发育。这篇综述旨在通过总结目前关于这些小脯氨酸异构酶蛋白的所有知识，激发对Par14和Par17的进一步研究，它们在大量关于Pin1的文献的掩盖下，是被忽视的药物靶点。
