Differential mitotic degradation of the CDC25B phosphatase variants
| Autor: | Estelle Schmitt, I Kieffer, Christine Dozier, Bernard Ducommun, Corinne Lorenzo |
|---|---|
| Přispěvatelé: | Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération (LBCMCP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Cancer Research
MESH: Fluorescence Resonance Energy Transfer Beta-Transducin Repeat-Containing Proteins Cyclin B Mitosis Polo-like kinase [SDV.BC]Life Sciences [q-bio]/Cellular Biology Mice 03 medical and health sciences MESH: Protein Structure Tertiary 0302 clinical medicine MESH: cdc25 Phosphatases CDC2 Protein Kinase Fluorescence Resonance Energy Transfer Genetics Animals Humans cdc25 Phosphatases MESH: Animals Cyclin B1 MESH: Metaphase Molecular Biology Metaphase MESH: Mice 030304 developmental biology 0303 health sciences MESH: Humans biology MESH: Cyclin B Cell cycle MESH: Mitosis beta-Transducin Repeat-Containing Proteins MESH: CDC2 Protein Kinase MESH: beta-Transducin Repeat-Containing Proteins Protein Structure Tertiary Cell biology MESH: Hela Cells Biochemistry Mitotic exit 030220 oncology & carcinogenesis biology.protein HeLa Cells |
| Zdroj: | Oncogene Oncogene, Nature Publishing Group, 2007, 26 (57), pp.7847-58. ⟨10.1038/sj.onc.1210596⟩ |
| ISSN: | 0950-9232 1476-5594 |
| DOI: | 10.1038/sj.onc.1210596⟩ |
| Popis: | CDC25 phosphatases control cell-cycle progression by dephosphorylating and activating cyclin-dependent kinases. CDC25B, one of the three members of this family in human cells, is thought to regulate initial mitotic events. CDC25B is an unstable protein whose proteasomal degradation is proposed to be controlled by beta-TrCP. Here, we have investigated the regulation of CDC25B during mitosis, using time-lapse video microscopy. We found that CDC25B expression is high during early mitosis, and that its degradation occurs after the metaphase-anaphase transition and cyclin B1 destruction. We also show that CDC25B degradation after metaphase is dependent on the integrity of the KEN-box and RRKSE motifs that are located within the alternatively spliced B domain, and that the CDC25B2 splice variant, that lacks this domain, is stable during mitosis. Furthermore, we show that the N-terminal region of CDC25B, encompassing the B domain, undergoes major conformational changes during mitosis that can be monitored by intramolecular fluorescence resonance energy transfer variation of specific CDC25B biosensors. This study demonstrates that CDC25B splice variants have differential mitotic stabilities, a feature that is likely to have major consequences on the local control of cyclin-dependent kinase-cyclin activities during mitotic progression. |
| Databáze: | OpenAIRE |
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