Mixed-lineage kinase 3 phosphorylates prolyl-isomerase Pin1 to regulate its nuclear translocation and cellular function
| Autor: | Velusamy Rangasamy, James S. Malter, Kun Ping Lu, Joanna C. Bakowska, Subhasis Das, Guri Tzivion, Rajakishore Mishra, Anumantha G. Kanthasamy, Tae Ho Lee, Gautam Sondarva, Ajay Rana, Basabi Rana |
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| Rok vydání: | 2012 |
| Předmět: |
Green Fluorescent Proteins
Active Transport Cell Nucleus Breast Neoplasms Biology Catalysis Serine Prolyl isomerase Humans Cyclin D1 Protein phosphorylation Phosphorylation Nuclear protein Cell Nucleus Centrosome Peptidylprolyl isomerase Multidisciplinary MAP kinase kinase kinase Cell Cycle Peptidylprolyl Isomerase Biological Sciences Cell cycle MAP Kinase Kinase Kinases Cell biology NIMA-Interacting Peptidylprolyl Isomerase Cell Transformation Neoplastic HEK293 Cells Biochemistry PIN1 Female HeLa Cells Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences. 109:8149-8154 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1200804109 |
| Popis: | Nuclear protein peptidyl-prolyl isomerase Pin1-mediated prolyl isomerization is an essential and novel regulatory mechanism for protein phosphorylation. Therefore, tight regulation of Pin1 localization and catalytic activity is crucial for its normal nuclear functions. Pin1 is commonly dysregulated during oncogenesis and likely contributes to these pathologies; however, the mechanism(s) by which Pin1 catalytic activity and nuclear localization are increased is unknown. Here we demonstrate that mixed-lineage kinase 3 (MLK3), a MAP3K family member, phosphorylates Pin1 on a Ser138 site to increase its catalytic activity and nuclear translocation. This phosphorylation event drives the cell cycle and promotes cyclin D1 stability and centrosome amplification. Notably, Pin1 pSer138 is significantly up-regulated in breast tumors and is localized in the nucleus. These findings collectively suggest that the MLK3-Pin1 signaling cascade plays a critical role in regulating the cell cycle, centrosome numbers, and oncogenesis. |
| Databáze: | OpenAIRE |
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