Department of Biological Sciences, Faculty of Science, National University of Singapore, 14 Science Drive 4, Singapore 117543.
Trends Biochem Sci. 2011 Oct;36(10):501-14. doi: 10.1016/j.tibs.2011.07.001. Epub 2011 Aug 17.
Pin1 is a highly conserved enzyme that only isomerizes specific phosphorylated Ser/Thr-Pro bonds in certain proteins, thereby inducing conformational changes. Such conformational changes represent a novel and tightly controlled signaling mechanism regulating a spectrum of protein activities in physiology and disease; often through phosphorylation-dependent, ubiquitin-mediated proteasomal degradation. In this review, we summarize recent advances in elucidating the role and regulation of Pin1 in controlling protein stability. We also propose a mechanism by which Pin1 functions as a molecular switch to control the fates of phosphoproteins. We finally stress the need to develop tools to visualize directly Pin1-catalyzed protein conformational changes as a way to determine their roles in the development and treatment of human diseases.
Pin1 是一种高度保守的酶，仅能使某些蛋白质中特定的磷酸化 Ser/Thr-Pro 键发生异构化，从而诱导构象变化。这种构象变化代表了一种新颖且严格控制的信号转导机制，可调节生理和疾病过程中一系列蛋白质活性；通常通过磷酸化依赖性、泛素介导的蛋白酶体降解来实现。在这篇综述中，我们总结了阐明 Pin1 在控制蛋白质稳定性方面的作用和调控的最新进展。我们还提出了一种机制，即 Pin1 作为分子开关来控制磷酸化蛋白命运。最后，我们强调需要开发工具来直接可视化 Pin1 催化的蛋白质构象变化，以确定它们在人类疾病的发生和治疗中的作用。
