Elucidating cdc25's Oncogenic Mechanism in Breast Cancer Using Pin1, a Negative Mitotic Regulator
Annual summary 1 Jun 1998-30 Jun 2001
DUKE UNIV MEDICAL CENTER DURHAM NC
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Isolation and cloning of a conserved cdc25-interacting protein, Pinl, provides the opportunity to explore the role of this binding partner in cooperating with cdc25 to regulate cell cycle transitions. Pinl is a peptidyl prolyl cis-trans isomerase its yeast homologue is essential for proper execution of mitosis and has implied roles in regulating transcription through its effects on chromatin structure and RNA processing. Presented here are data that demonstrate a role for Pinl in negatively regulating the mitotic entry in Xenopus laevis. Without catalytically active Pinl, egg extracts initiate mitosis prematurely and do not activate the G2 checkpoint that arrests the cell cycle when DNA replication is stalled. Because it selectively binds to and catalyzes isomerization of prolines preceded by phosphorylated serine or threonine, Pinl may exert its inhibitory influence on mitotic entry by affecting phosphoprotein structure. Together with the work of other groups, this study suggests a role for Pinl in controlling the timing of mitotic entry by isomerizing phospho-ST-proline subsequences and thereby influencing the abilities of these motifs to be substrates for the mitotic phosphatase, cdc25.
- Medicine and Medical Research