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Transcriptome analysis of NCC-IT-A3 cells by Barasertib treatment

ABSTRACT: During mitosis, the chromosomal passenger complex (CPC) that is formed by Aurora-B, INCENP, Survivin, and Borealin ensures the faithful segregation of the chromosomes into daughter cells. We previously have shown that CPC activity was terminated by the anaphase promoting complex/cyclosome (APC/C) and its cofactor Cdh1 via ubiquitylation of Borealin and Aurora-B during the G1 phase of somatic cells. On the other hand, protein levels of Borealin and Aurora-B were stable during cell cycle progression due to high levels of Emi1, which keep APC/CCdh1 inactive in embryonal carcinoma (EC) cells. During retinoic acid-induced differentiation of EC cells, these proteins were downregulated by APC/CCdh1-mediated ubiquitylation. Interestingly, CPC proteins form a complex with Aurora-B kinase activity even in interphase of EC cells. Significantly, inhibition of CPC activity by either knockdown of Borealin or Aurora-B and Aurora-B kinase inhibitor treatment induced spontaneous differentiation of EC cells. In conclusion, sustained CPC activity plays a critical role in maintenance of the undifferentiated state of pluripotent stem cells. We therefore propose an interphase role of the CPC in regulating embryonic pluripotency.

ORGANISM(S): Homo sapiens

PROVIDER: GSE179503 | GEO | 2021/07/09

REPOSITORIES: GEO

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Regulated interaction of ID2 with the anaphase-promoting complex links progression through mitosis with reactivation of cell-type-specific transcription

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2022-03-11 | GSE181639 | GEO

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Ordered dephosphorylation initiated by the selective proteolysis of cyclin B drives mitotic exit

Project description:APC/C-mediated proteolysis of cyclin B and securin promotes entry into anaphase, inactivating CDK1 and permitting chromosome segregation, respectively. Reduction of CDK1 activity relieves inhibition of the CDK1-opposing phosphatases PP1 and PP2A-B55 leading to dephosphorylation of substrates crucial for mitotic exit. Meanwhile, continued APC/C activity is required to target various proteins, including Aurora and Polo kinases, for degradation. Together, these activities orchestrate a complex series of events during mitotic exit. However, the relative importance of regulated proteolysis and dephosphorylation in dictating the order and timing of these events remains unclear. Using high temporal-resolution mass spectrometry, we compare the relative extent of proteolysis and protein dephosphorylation. This reveals highly-selective rapid (~5min half-life) proteolysis of cyclin B, securin and geminin at the metaphase to anaphase transition, followed by slow proteolysis (>60 min half-life) of other mitotic regulators. Protein dephosphorylation requires APC/C-dependent destruction of cyclin B and was resolved into PP1-dependent fast, intermediate and slow categories with unique sequence motifs. We conclude that dephosphorylation initiated by the selective proteolysis of cyclin B drives the bulk of changes observed during mitotic exit.

2020-09-04 | PXD019795 | Pride

Ordered dephosphorylation initiated by the selective proteolysis of cyclin B drives mitotic exit

2020-09-04 | PXD019788 | Pride

Ordered dephosphorylation initiated by the selective proteolysis of cyclin B drives mitotic exit

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2020-09-04 | PXD019791 | Pride

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2018-09-19 | PXD006335 | Pride

Anaphase-promoting complex-dependent control of cell identity

Project description:Tissue development and homeostasis rely on the proliferation of progenitor cells, whose identities are established by tightly controlled gene expression networks. However, mRNA synthesis is inhibited during mitosis, and the transcriptional programs that define a cell type must be restarted upon entry into each new cell cycle; how this is accomplished is poorly understood. Here, we identified a ubiquitin-dependent mechanism that integrates gene expression with cell division to preserve cell identity. We found that WDR5 and TBP, which bind active promoters during interphase, recruit the E3 ligase anaphase-promoting complex (APC/C) to specific transcription start sites during mitosis. This allows the APC/C to locally decorate histones with K11/K48-linked ubiquitin chains, which destabilizes nucleosomes and ensures continued gene expression in the next cell cycle. Mitotic exit and transcription re-initiation are therefore controlled by the same essential regulator, the APC/C, which provides a robust mechanism to maintain cell identity through cell division.

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