Sequence-Specific and Phosphorylation-Dependent Proline Isomerization: A Potential Mitotic Regulatory Mechanism

• Published in: Science (American Association for the Advancement of Science) Vol. 278; no. 5345; pp. 1957 - 1960
• Main Authors: Yaffe, Michael B., Schutkowski, Mike, Shen, Minhui, Zhou, Xiao Zhen, Stukenberg, P. Todd, Rahfeld, Jens-Ulrich, Xu, Jian, Kuang, Jian, Kirschner, Marc W., Fischer, Gunter, Cantley, Lewis C., Lu, Kun Ping
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 12.12.1997; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Amino Acid Isomerases - metabolism; Amino acids; Antibodies; Antibodies, Monoclonal; Antigens; Binding Sites; Biological and medical sciences; Carrier Proteins - metabolism; Cell cycle; Cell Cycle Proteins - chemistry; Cell Cycle Proteins - metabolism; Cell cycle, cell proliferation; Cell physiology; DNA-Binding Proteins - metabolism; Enzymes; Epitopes; Fundamental and applied biological sciences. Psychology; Heat-Shock Proteins - metabolism; HeLa Cells; Humans; Isomerism; Isomerization; Libraries; Medical research; Mitosis; Models, Molecular; Molecular and cellular biology; Narcotics; NIMA-Interacting Peptidylprolyl Isomerase; Observations; Oligopeptides - chemistry; Oligopeptides - metabolism; Peptide Library; Peptides; Peptidylprolyl Isomerase - chemistry; Peptidylprolyl Isomerase - metabolism; Phosphates; Phosphoproteins - chemistry; Phosphoproteins - immunology; Phosphoproteins - metabolism; Phosphorylation; Phosphoserine - metabolism; Phosphothreonine - metabolism; Proline - metabolism; Protein Conformation; Protein kinases; Proteins; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - metabolism; Substrate Specificity; Tacrolimus Binding Proteins; Human; Sequence specificity; Peptidylprolyl isomerase; Phosphorylation; Molecular structure; Enzyme; Mitosis; Molecular interaction; Regulation(control); Isomerases; Cell line; Enzymatic activity; cis-trans-Isomerases
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.278.5345.1957

Pin1 is an essential and conserved mitotic peptidyl-prolyl isomerase (PPIase) that is distinct from members of two other families of conventional PPIases, cyclophilins and FKBPs (FK-506 binding proteins). In response to their phosphorylation during mitosis, Pin1 binds and regulates members of a highly conserved set of proteins that overlaps with antigens recognized by the mitosis-specific monoclonal antibody MPM-2. Pin1 is here shown to be a phosphorylation-dependent PPIase that specifically recognizes the phosphoserine-proline or phosphothreonine-proline bonds present in mitotic phosphoproteins. Both Pin1 and MPM-2 selected similar phosphorylated serine-proline-containing peptides, providing the basis for the specific interaction between Pin1 and MPM-2 antigens. Pin1 preferentially isomerized proline residues preceded by phosphorylated serine or threonine with up to 1300-fold selectivity compared with unphosphorylated peptides. Pin1 may thus regulate mitotic progression by catalyzing sequence-specific and phosphorylation-dependent proline isomerization.