Sequence-specific and phosphorylation-dependent proline isomerization: A potential mitotic regulatory mechanism

被引:697
作者
Yaffe, MB
Schutkowski, M
Shen, MH
Zhou, XZ
Stukenberg, PT
Rahfeld, JU
Xu, J
Kuang, J
Kirschner, MW
Fischer, G
Cantley, LC
Lu, KP
机构
[1] BETH ISRAEL DEACONESS MED CTR, DEPT MED, DIV HEMATOL ONCOL, CANC BIOL PROGRAM, BOSTON, MA 02215 USA
[2] BETH ISRAEL DEACONESS MED CTR, DIV SIGNAL TRANSDUCT, DEPT MED, BOSTON, MA 02215 USA
[3] BETH ISRAEL DEACONESS MED CTR, DEPT SURG, BOSTON, MA 02215 USA
[4] MAX PLANCK RES UNIT ENZYMOL PROT FOLDING, D-06120 HALLE, GERMANY
[5] HARVARD UNIV, SCH MED, DEPT CELL BIOL, BOSTON, MA 02115 USA
[6] UNIV TEXAS, MD ANDERSON CANC CTR, DEPT CLIN INVEST, HOUSTON, TX 77030 USA
[7] HARVARD UNIV, SCH MED, DIV AGING, BOSTON, MA 02215 USA
关键词
D O I
10.1126/science.278.5345.1957
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Pin1 is an essential and conserved mitotic peptidyl-prolyl isomerase (PPlase) that is distinct from members of two other families of conventional PPlases, 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 protein; that overlaps with antigens recognized by the mitosis-specific monoclonal antibody MPM-2. Pin1 is here shown to be a phosphorylation-dependent PPlase 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.
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页码:1957 / 1960
页数:4
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