Hu Xiangming, Chen Lin-Feng
Fujian Key Laboratory for Translational Research in Cancer and Neurodegenerative Diseases, Institute for Translational Medicine, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL, United States.
Front Cell Dev Biol. 2020 Mar 20;8:179. doi: 10.3389/fcell.2020.00179. eCollection 2020.
Pin1 is a peptidyl-prolyl isomerase that specifically binds to a phosphorylated serine or threonine residue preceding a proline (pSer/Thr-Pro) motif and catalyzes the isomerization of proline imidic peptide bond, resulting in conformational change of its substrates. Pin1 regulates many biological processes and is also involved in the development of human diseases, like cancer and neurological diseases. Many Pin1 substrates are transcription factors and transcription regulators, including RNA polymerase II (RNAPII) and factors associated with transcription initiation, elongation, termination and post-transcription mRNA decay. By changing the stability, subcellular localization, protein-protein or protein-DNA/RNA interactions of these transcription related proteins, Pin1 modulates the transcription of many genes related to cell proliferation, differentiation, apoptosis and immune response. Here, we will discuss how Pin regulates the properties of these transcription relevant factors for effective gene expression and how Pin1-mediated transcription contributes to the diverse pathophysiological functions of Pin1.
Pin1是一种肽基脯氨酰异构酶，它特异性结合脯氨酸（pSer/Thr-Pro）基序之前的磷酸化丝氨酸或苏氨酸残基，并催化脯氨酸亚胺肽键的异构化，导致其底物的构象变化。Pin1调节许多生物学过程，还参与人类疾病的发展，如癌症和神经疾病。许多Pin1底物是转录因子和转录调节因子，包括RNA聚合酶II（RNAPII）以及与转录起始、延伸、终止和转录后mRNA衰变相关的因子。通过改变这些转录相关蛋白的稳定性、亚细胞定位、蛋白质-蛋白质或蛋白质-DNA/RNA相互作用，Pin1调节许多与细胞增殖、分化、凋亡和免疫反应相关基因的转录。在这里，我们将讨论Pin如何调节这些转录相关因子的特性以实现有效的基因表达，以及Pin1介导的转录如何促成Pin1的多种病理生理功能。
