Proline-directed phosphorylation and isomerization in mitotic regulation and in Alzheimer's Disease.
The reversible phosphorylation of proteins on serine/threonine residues preceding proline (Ser/Thr-Pro) is a major regulatory mechanism for the control of a series of cell cycle events. Although phosphorylation is thought to regulate protein function by inducing conformational changes, little is known about most of these conformational changes and their significance. Recent studies indicate that the conformation and function of a subset of these phosphorylated proteins are controlled by the prolyl isomerase Pin1 through isomerization of specific phosphorylated Ser/Thr-Pro bonds. Furthermore, compelling evidence supports the idea that proline-directed phosphorylation and subsequent isomerization play a critical role not only in cell cycle control, but also in the development of Alzheimer's disease, where postmitotic neurons display various cell cycle markers, especially mitotic events, prior to degeneration.
Lu
Kun Ping
KP
Cancer Biology Program, Beth Israel Deaconess Medical Center, Harvard Medical School, USA. klu@caregroup.harvard.edu
Liou
Yih-Cherng
YC
Vincent
Inez
I
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007536:Isomerism; D008938:Mitosis / Q000502:physiology*; D008959:Models, Neurological; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D019696:Peptidylprolyl Isomerase / Q000378:metabolism; D010766:Phosphorylation; D011392:Proline / Q000378:metabolism*
D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D011392:Proline; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase