Phosphorylation-dependent prolyl isomerization: a novel cell cycle regulatory mechanism.
Protein phosphorylation by proline-directed protein kinases plays an essential role in triggering a programmed set of cell cycle events. We have recently isolated an essential and conserved mitotic regulator, Pin1. Pin1 is a phosphorylation-dependent prolyl isomerase that specifically isomerizes the phosphorylated serine/threonine-proline bond. Pin1 also binds and regulates the function of a conserved set of mitosis-specific phosphoproteins. These results suggest phosphorylation-dependent prolyl isomerization to be a novel cell cycle regulatory mechanism. This new post-translational regulation may allow the general increase in protein phosphorylation to be converted into the organised and programmed set of structural modifications that occur during mitosis. In addition, since inhibition of Pin1 induces mitotic arrest and apoptosis, Pin1 may be a potential new drug target.
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Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002453:Cell Cycle / Q000502:physiology*; D006801:Humans; D008938:Mitosis / Q000502:physiology; D008969:Molecular Sequence Data; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000737:chemistry / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D010769:Phosphothreonine / Q000378:metabolism; D011487:Protein Conformation
D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D010750:Phosphoproteins; D010769:Phosphothreonine; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase