Pinning down cell signaling, cancer and Alzheimer's disease.
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.
Lu
Kun Ping
KP
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. klu@bidmc.harvard.edu
D000544:Alzheimer Disease / Q000503:physiopathology*; D042846:CDC2-CDC28 Kinases / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D051357:Cyclin-Dependent Kinase 2; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009369:Neoplasms / Q000503:physiopathology*; D019696:Peptidylprolyl Isomerase / Q000737:chemistry / Q000502:physiology*; D010766:Phosphorylation; D010768:Phosphoserine / Q000737:chemistry / Q000378:metabolism; D010769:Phosphothreonine / Q000737:chemistry / Q000378:metabolism; D011392:Proline / Q000737:chemistry / Q000378:metabolism; D038461:Proline-Directed Protein Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000502:physiology*
D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D010769:Phosphothreonine; D010768:Phosphoserine; D011392:Proline; D038461:Proline-Directed Protein Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase