Phosphorylation of SAF-A/hnRNP-U Serine 59 by Polo-Like Kinase 1 Is Required for Mitosis
| Autor: | Ruiqiong Ye, Sébastien Britton, Pauline Douglas, Nicholas A. Morrice, Laura Trinkle-Mulcahy, Susan P. Lees-Miller |
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| Rok vydání: | 2015 |
| Předmět: |
Paclitaxel
Mitosis Cell Cycle Proteins Heterogeneous-Nuclear Ribonucleoprotein U Polo-like kinase Protein Serine-Threonine Kinases Biology environment and public health PLK1 APC/C activator protein CDH1 G2 phase Cell Line Tumor Proto-Oncogene Proteins CDC2 Protein Kinase Phosphoprotein Phosphatases Humans Protein Phosphatase 2 Cyclin B1 Phosphorylation RNA Small Interfering Molecular Biology Serine/threonine-specific protein kinase Nocodazole fungi Articles Cell Biology Protein phosphatase 2 Cyclin-Dependent Kinases Tubulin Modulators Cell biology Securin enzymes and coenzymes (carbohydrates) Biochemistry RNA Interference DNA Damage HeLa Cells |
| Zdroj: | Molecular and Cellular Biology. 35:2699-2713 |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/mcb.01312-14 |
| Popis: | Scaffold attachment factor A (SAF-A), also called heterogenous nuclear ribonuclear protein U (hnRNP-U), is phosphorylated on serine 59 by the DNA-dependent protein kinase (DNA-PK) in response to DNA damage. Since SAF-A, DNA-PK catalytic subunit (DNA-PKcs), and protein phosphatase 6 (PP6), which interacts with DNA-PKcs, have all been shown to have roles in mitosis, we asked whether DNA-PKcs phosphorylates SAF-A in mitosis. We show that SAF-A is phosphorylated on serine 59 in mitosis, that phosphorylation requires polo-like kinase 1 (PLK1) rather than DNA-PKcs, that SAF-A interacts with PLK1 in nocodazole-treated cells, and that serine 59 is dephosphorylated by protein phosphatase 2A (PP2A) in mitosis. Moreover, cells expressing SAF-A in which serine 59 is mutated to alanine have multiple characteristics of aberrant mitoses, including misaligned chromosomes, lagging chromosomes, polylobed nuclei, and delayed passage through mitosis. Our findings identify serine 59 of SAF-A as a new target of both PLK1 and PP2A in mitosis and reveal that both phosphorylation and dephosphorylation of SAF-A serine 59 by PLK1 and PP2A, respectively, are required for accurate and timely exit from mitosis. |
| Databáze: | OpenAIRE |
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