Lu Kun Ping
Cancer Biology Program, Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, NRB 1030K, Boston, MA 02215, USA.
Trends Biochem Sci. 2004 Apr;29(4):200-9. doi: 10.1016/j.tibs.2004.02.002.
Protein phosphorylation on certain serine or threonine residues preceding proline (Ser/Thr-Pro) is a pivitol signaling mechanism in diverse cellular processes and its deregulation can lead to human disease. However, little is known about how these phosphorylation events actually control cell signaling. Pin1 is a highly conserved enzyme that isomerizes only the phosphorylated Ser/Thr-Pro bonds in certain proteins, thereby inducing conformational changes. Recent results indicate that such conformational changes following phosphorylation are a novel signaling mechanism pivotal in regulating many cellular functions. This mechanism also offers new insights into the pathogenesis and treatment of human disease, most notably cancer and Alzheimer's disease. Thus, Pin1 plays a key role in linking signal transduction to the pathogenesis of cancer and Alzheimer's disease - two major age-related diseases.
脯氨酸之前特定丝氨酸或苏氨酸残基上的蛋白质磷酸化(Ser/Thr-Pro)是多种细胞过程中的关键信号传导机制,其失调会导致人类疾病。然而,对于这些磷酸化事件如何实际控制细胞信号传导,人们了解甚少。Pin1是一种高度保守的酶,它仅使某些蛋白质中磷酸化的Ser/Thr-Pro键异构化,从而诱导构象变化。最近的结果表明,磷酸化后的这种构象变化是调节许多细胞功能的关键新信号传导机制。该机制还为人类疾病,尤其是癌症和阿尔茨海默病的发病机制和治疗提供了新见解。因此,Pin1在将信号转导与癌症和阿尔茨海默病(两种主要的与年龄相关的疾病)的发病机制联系起来方面起着关键作用。