bims-micesi Biomed News
on Mitotic cell signalling
Issue of 2025–11–16
twelve papers selected by
Valentina Piano, Uniklinik Köln
  1. The Dynamics of the ESCRT Machinery in Open Mitosis from Physiology to Pathology.
  2. Mitotic entry is controlled by the plant-specific phosphatase BSL1 and cyclin-dependent kinase B.
  3. Condensin-Condensin Interactions Facilitate Mitotic Chromosome Assembly in Xenopus Egg Extracts.
  4. Adapting plasma membrane for mitotic cell rounding through Aurora A phosphorylation of numb.
  5. The Impact of Golgi Organization on Cell Cycle and Cancer Development.
  6. SOX2 phosphorylation during mitosis limits genomic damage.
  7. KIF18A promotes chromosome congression in cooperation with CENP-E downstream of CENP-C.
  8. Dynamic crotonylation of Bub3 regulates mitotic checkpoint silencing and chromosome segregation.
  9. Chemical Genetics with SP600125 Reveals That Mps1 Protein Kinase Works as a Regulatory Element in Post-embryonic Development of the Arabidopsis thaliana Root SystemAn Insight into Plant Cell Cycle Control.
  10. Substrate recognition by human separase.
  11. Cohesin reconstitution and homologous recombination repair of DNA double-strand breaks in late mitosis.
  12. High-content phenotyping reveals Golgi dynamics and their role in cell cycle regulation.
  1. Cells. 2025 Oct 27. pii: 1681. [Epub ahead of print]14(21):
    The Dynamics of the ESCRT Machinery in Open Mitosis from Physiology to Pathology.
    Mattia La Torre, Federica Cannistrà, Romina Burla, Isabella Saggio.
      The Endosomal Sorting Complex Required for Transport (ESCRT) is a highly conserved machinery best known for its role in endosomal trafficking and membrane remodeling. Increasing evidence shows that ESCRT components are also key regulators during open mitosis, where precise membrane dynamics are essential for nuclear envelope reformation and spindle disassembly. In this review, we explore how the ESCRT machinery coordinates mitotic processes under physiological conditions and how their dysregulation contributes to genomic instability, altered cell division, and disease. We highlight recent findings on the spatiotemporal control of ESCRT recruitment at mitotic membranes, the interplay with chromatin and nuclear envelope-associated factors, and the consequences of defective ESCRT function in pathological contexts such as cancer and neurodegeneration. By connecting molecular mechanisms with cellular outcomes, we provide an integrated view of how the ESCRT machinery acts as critical guardian of mitotic fidelity and offer some routes for the identification of potential therapeutic targets in human disease.
    Keywords:  cancer; cell division; cell migration; neurodegeneration; nuclear membrane; nucleopathies
    DOI:  https://doi.org/10.3390/cells14211681
  2. Nat Plants. 2025 Nov 13.
    Mitotic entry is controlled by the plant-specific phosphatase BSL1 and cyclin-dependent kinase B.
    Frej Tulin, Yalikunjiang Aizezi, Andres V Reyes, Yuji Fujieda, Arthur Grossman, Shou-Ling Xu, Masayuki Onishi, Farhah F Assaad, Zhi-Yong Wang.
      Cell cycle regulation is well understood in opisthokonts (fungi and metazoans) but not in plants or Apicomplexa, as some cell cycle regulators are not conserved. In opisthokonts, cell cycle progression requires the dephosphorylation of cyclin-dependent kinase (CDK) by the CDC25 phosphatase. Plants have no CDC25, and thus their mechanisms of cell cycle regulation remain elusive. Here we show that the BSL1 phosphatase dephosphorylates CDKB1 to promote mitotic entry in Chlamydomonas. Alterations of BSL1 or CDKB1 block mitotic entry after DNA replication. BSL1 shows dynamic localization through the cell cycle at the basal bodies, spindle poles and cleavage furrow. CDKB1 is hyperphosphorylated at the Thr14 and Tyr15 residues in the bsl1 mutant and in wild-type cells treated with DNA replication inhibitors. BSL1 binds to CDKB1 and dephosphorylates CDKB1 pThr14/pTyr15 in vitro. Phospho-mimicking alterations of Thr14/Tyr15 inactivate CDKB1 function, whereas phospho-blocking alterations cause sensitivity to DNA replication inhibitors, which delay cytokinesis in wild-type cells more than in cells expressing unphosphorylatable mutant CDKB1. These results indicate that CDKB1 Thr14 and Tyr15 are phosphorylated to block mitotic entry before DNA replication is complete, and BSL1 dephosphorylates CDKB1 to promote mitosis. Our study demonstrates that BSL1, a phosphatase conserved in plants and Apicomplexa but absent in fungi and animals, is a CDKB1-activating mitosis-promoting factor that has evolved additional signalling functions in receptor kinase pathways in higher plants.
    DOI:  https://doi.org/10.1038/s41477-025-02145-z
  3. Genes Cells. 2025 Nov;30(6): e70065
    Condensin-Condensin Interactions Facilitate Mitotic Chromosome Assembly in Xenopus Egg Extracts.
    Kazuhisa Kinoshita, Yuuki Aizawa, Tatsuya Hirano.
      Condensins are large protein complexes that play a central role in mitotic chromosome assembly in eukaryotes. Our previous mutational analyses of condensin I, combined with Xenopus egg cell-free extracts, provided evidence that dynamic condensin-condensin interactions, triggered by a contact between the CAP-D2 and SMC4 subunits, underlie proper chromosome assembly and shaping. To examine whether and how the hypothesized condensin-condensin interactions contribute to chromosome assembly, here we employed a rapamycin-inducible FKBP-FRB dimerization system to artificially tether CAP-D2 and SMC4 either between different complexes (inter-complex tethering) or within single complexes (intra-complex tethering). The ability of the resulting complexes to assemble mitotic chromosomes was then assessed in Xenopus egg extracts. We found that inter-complex tethering enhances condensin I loading and facilitates mitotic chromosome assembly, whereas intra-complex tethering restricts its function. Moreover, deficiencies in the D2-SMC4 contact caused by an SMC4 W-loop mutation were partially compensated by inter-complex tethering. Together, these findings provide direct evidence that condensin-condensin interactions facilitate mitotic chromosome assembly.
    Keywords:  SMC ATPase; Xenopus egg extracts; chromosome assembly; condensins; loop extrusion; mitosis
    DOI:  https://doi.org/10.1111/gtc.70065
  4. J Cell Biol. 2025 Dec 01. pii: e202412005. [Epub ahead of print]224(12):
    Adapting plasma membrane for mitotic cell rounding through Aurora A phosphorylation of numb.
    Yanyan Li, Ke Liu, Xian Lin, Zhihao Ding, Haiyan Sun, Xiangyun Liao, Binghua Cheng, Wenli Shi, Junde Xu, Jiaming Liang, Zeyu Zhou, Wenjie Zhou, Hui Tian, Long Meng, Guangyong Chen, Ximing Shao, Hongchang Li.
      Cell rounding during mitosis necessitates adaptive remodeling of plasma membrane and cortical cytoskeleton. However, the underlying mechanisms remain poorly elucidated. Here, we have identified Numb phosphorylation as a pivotal mechanism in the membrane-cytoskeleton remodeling associated with mitotic cell rounding. Upon mitotic entry, Aurora A phosphorylates Numb, leading to the dissociation of Numb from plasma membrane. This is crucial for proper plasma membrane retraction, since overexpression of a non-phosphorylatable mutant or a constitutively membrane-bound variant of Numb dramatically disrupts mitotic plasma membrane retraction. Mechanistically, releasing Numb from the plasma membrane enhances the myosin I-mediated membrane-to-cortex adhesion, thereby facilitating the plasma membrane retraction accompanied with cytoskeletal withdrawal. Further analysis showed that compromised plasma membrane retraction confines mitotic cell rounding and consequently leads to spindle orientation defects. Thus, our study elucidates a phosphorylation-mediated mechanism underlying plasma membrane retraction and underscores the functional importance of this process in the context of mitotic cell rounding.
    DOI:  https://doi.org/10.1083/jcb.202412005
  5. Subcell Biochem. 2026 ;110 109-148
    The Impact of Golgi Organization on Cell Cycle and Cancer Development.
    Antonino Colanzi, Inmaculada Ayala.
      The Golgi complex plays a pivotal role in the secretory pathway, cell signaling, and cytoskeleton organization. In mammalian cells, it is organized as a ribbon-like structure that can undergo dynamic reorganizations, which are crucial for various cellular processes, including mitosis and cell migration. During mitosis, the Golgi complex is subjected to a tightly regulated disassembly process, essential for proper cell division, while its reformation is critical for inheritance by daughter cells. Disruption of Golgi organization has been linked to pathological conditions, including cancer, as altered organization and function can contribute to tumor progression by impacting glycosylation, cell polarity, and extracellular matrix remodeling. This chapter explores the molecular mechanisms regulating Golgi disassembly during the cell cycle and its involvement in ensuring proper cell division. Additionally, we discuss the emerging understanding of the potential role of modifications of the Golgi organization in tumor development and metastasis. Collectively, the findings presented in this chapter underscore the physiological significance of the Golgi ribbon structure and the pathological implications of its alterations in cancer progression, which could offer novel therapeutic opportunities for cancer treatment.
    Keywords:  Centrosome; Checkpoint; Golgi complex; Mitosis; Mitotic spindle; Ribbon
    DOI:  https://doi.org/10.1007/978-3-032-06936-8_6
  6. Genes Dev. 2025 Nov 10.
    SOX2 phosphorylation during mitosis limits genomic damage.
    Charles A C Williams, Dounia Djeghloul, Nicolas Veland, Alhafidz Hamdan, Maria Kalantzaki, Erika Lo, Robert Illingworth, Alex Von Kriegsheim, Amanda G Fisher, Abdenour Soufi, Steven M Pollard.
      Pioneer transcription factors (TFs) such as SOX2 play critical roles in the control of stem cell identity and are dysregulated in many human cancers. For example, SOX2 regulates the self-renewal of neural stem cells (NSCs) and is typically highly expressed in glioblastoma stem cells (GSCs), where it is known to induce an immature NSC-like state. Here, we explored the regulation of SOX2 by phosphorylation during NSC division and identified an unexpected role for excessive SOX2 pioneer activity in driving mitotic damage. We found that SOX2 phosphorylation during mitosis is a key switch that prevents promiscuous chromatin binding across the genome. Without this regulatory control, excessive SOX2 in mitosis triggers chromatin opening, resulting in increased mitotic transit times and increased chromosomal damage. Therefore, elevated levels of SOX2 in cancers may have dual oncogenic roles: inducing stemness during interphase via its well-known transcriptional roles but simultaneously promoting chromosomal disruptions through unconstrained pioneer factor activity.
    Keywords:  DNA damage; SOX2; heterochromatin; mitosis; mitotic bookmarking; neural stem cell; phosphorylation; transcription
    DOI:  https://doi.org/10.1101/gad.352664.125
  7. Cell Rep. 2025 Nov 10. pii: S2211-1247(25)01286-0. [Epub ahead of print] 116515
    KIF18A promotes chromosome congression in cooperation with CENP-E downstream of CENP-C.
    Jiahang Miao, Masatoshi Hara, Kuan-Chung Su, Heather R Keys, Weixia Kong, Yusuke Takenoshita, Iain M Cheeseman, Tatsuo Fukagawa.
      Chromosome congression is a key process that acts to align chromosomes at the spindle equator via kinetochore-microtubule interactions, with defects in chromosome alignment leading to chromosomal instability. However, defining the mechanisms that underlie chromosome congression is limited due to the multiple factors that act in parallel to regulate chromosome movement. Here, we conducted a genome-wide Cas9-based functional genetics screen using a hypomorphic CENP-C mutant that affects its kinetochore interactions. Our analysis identified KIF18A, whose knockout resulted in synthetic lethality with the CENP-C mutant. Further analysis revealed that the synthetic defect was due to a reduction in CENP-E function in the CENP-C mutant. Our work suggests that KIF18A promotes chromosome alignment in cooperation with CENP-E downstream of CENP-C during early prometaphase. Thus, our analysis enables us to dissect parallel molecular mechanisms for chromosome congression and identify sensitivities and biomarkers that might guide anti-KIF18A chemotherapeutics.
    Keywords:  CENP-C; CENP-E; CP: Molecular biology; KIF18A; KMN network; kinetochore
    DOI:  https://doi.org/10.1016/j.celrep.2025.116515
  8. J Mol Cell Biol. 2025 Nov 13. pii: mjaf040. [Epub ahead of print]
    Dynamic crotonylation of Bub3 regulates mitotic checkpoint silencing and chromosome segregation.
    Xufan Shi, Xingchen Yu, Wenwen Wang, Fangyuan Xiong, Xiao Yuan, Qing Hu, Xiaoyu Song, Zhen Dou, Xuebiao Yao, Liangyu Zhang.
      
    DOI:  https://doi.org/10.1093/jmcb/mjaf040
  9. ACS Omega. 2025 Nov 04. 10(43): 51900-51911
    Chemical Genetics with SP600125 Reveals That Mps1 Protein Kinase Works as a Regulatory Element in Post-embryonic Development of the Arabidopsis thaliana Root SystemAn Insight into Plant Cell Cycle Control.
    Emanuel Victor Nogueira Gotardo, Eduardo Alves Gamosa de Oliveira, Lucas Zanchetta Passamani, Izabela Silva Dos Santos, Geraldo de Amaral Gravina, Claudete Santa-Catarina, Vanildo Silveira, Antônia Elenir Amâncio Oliveira, Marco Antonio Lopes Cruz.
      The "spindle assembly checkpoint" (SAC) is a regulatory pathway that monitors the correct anchoring of the mitotic spindle microtubules to chromosomes during the metaphase-anaphase transition. The protein kinase monopolar spindle 1 (Mps1) is a key SAC component and is considered a promising target for antitumor drugs. This has led to the development of different inhibitory molecules that have helped to elucidate the Mps1 functions in the cell cycle. However, in plants, the catalytic mechanisms and roles of Mps1 during cell proliferation remain unknown. Here, we show that Arabidopsis thaliana's Mps1 (AtMps1) has a similar catalytic structure to that observed in humans (Homo sapiens' Mps1HsMps1) and that its inhibition by SP600125 hinders postgerminative development. Further, our computational docking studies strongly suggest that both HsMps1 and AtMps1 interact with SP600125 in a similar manner and that plant proteins have topologically conserved protein-protein interaction motifs in their kinase domains. Furthermore, using A. thaliana as an experimental model demonstrates that Mps1 activity is essential for cell proliferation and postgerminative development and that SP600125 effects are reversible. Our experiments open new possibilities for understanding the mechanisms of the Mps1 protein using plants as experimental models. They also show that chemical genetics is a robust alternative for studies of plant development.
    DOI:  https://doi.org/10.1021/acsomega.5c07325
  10. Sci Adv. 2025 Nov 14. 11(46): eady9807
    Substrate recognition by human separase.
    Jun Yu, Sophia Schmidt, Margherita Botto, Kitaik Lee, Chloe M Ghent, Jonah M Goodfried, Andrew Howe, Francis J O'Reilly, David O Morgan, Andreas Boland.
      The cohesin complex encircles sister chromatids in early mitosis. At anaphase onset, sister separation is triggered by the proteolytic cleavage of the cohesin subunit SCC1/RAD21 by separase. SCC1 contains two cleavage sites, where cleavage is stimulated by SCC1 phosphorylation. Substrate recognition and cleavage are only partly understood. Here, we determined structures of human separase in apo- or substrate-bound forms that, together with biochemical analysis, provide critical insights into separase cleavage regulation. We verify the first SCC1 cleavage site and reassign the second. We show that substrates, including separase autocleavage sites and the two SCC1 cleavage sites, interact with docking sites in separase, including five phosphate-binding sites. We also describe the interaction between the cohesin subunit SA1/SA2 and separase, which promotes cleavage at the second SCC1 site. Using cross-linking mass spectrometry and cryo-electron microscopy, we propose how cohesin is targeted by human separase. Our work provides an extensive functional and structural framework that explains a key event in cell division.
    DOI:  https://doi.org/10.1126/sciadv.ady9807
  11. Elife. 2025 Nov 11. pii: RP92706. [Epub ahead of print]13
    Cohesin reconstitution and homologous recombination repair of DNA double-strand breaks in late mitosis.
    Jessel Ayra Plasencia, Sara Medina-Suárez, Esperanza Hernández-Carralero, Jonay García-Luis, Lorraine S Symington, Félix Machín.
      The cohesin complex maintains sister chromatid cohesion from S phase to anaphase onset. Cohesin also plays roles in chromosome structure and DNA repair. In yeast, the cohesin subunit Scc1 is cleaved at anaphase onset to allow segregation in an orderly manner, although some residual cohesin subunits remain to maintain chromosome structure. Efficient DNA double-strand break (DSB) repair by homologous recombination (HR) with the sister chromatid also depends on cohesin. Here, we have examined the role of residual cohesin in DSB repair in telophase (late mitosis). We have found that Scc1 returns in telophase after DSBs and that it partially reconstitutes a chromatin-bound cohesin complex with Smc1 and an acetylated pool of Smc3 after a single HO-induced DSB at the MAT locus. However, this new cohesin is neither required for the HR-driven MAT switching nor binds to the MAT locus after the DSB.
    Keywords:  DNA double-strand break; MAT switching; S. cerevisiae; Scc1/Mcd1; anaphase; cell biology; chromosomes; cohesin; gene expression; homologous recombination
    DOI:  https://doi.org/10.7554/eLife.92706
  12. J Cell Biol. 2026 Jan 05. pii: e202503083. [Epub ahead of print]225(1):
    High-content phenotyping reveals Golgi dynamics and their role in cell cycle regulation.
    Xun Cao, Yiming Peng, Mengyuan Yang, Mengling Gan, Di Zhang, Shiyue Zhou, Daisuke Takao.
      Recent advances in quantitative bioimage analysis have enabled detailed analyses of cellular and subcellular morphological features, enhancing our understanding of cellular functions. Here, we introduce an image-based phenotyping pipeline designed for the comprehensive analysis of dynamic organelle morphology, particularly the Golgi apparatus and cilia, during cell cycle progression. Our approach emphasizes interpretable feature extraction, enabling detection of both prominent and subtle morphological changes. By using well-characterized morphological dynamics of intracellular structures as benchmarks, we demonstrated that our method can reliably detect established phenotypic changes and serves as a valid tool for quantitative profiling. Further investigation of the G0/G1 transition revealed an unexplored link between Golgi dynamics and ciliary disassembly. Specifically, inhibition of the G0/G1 transition correlated with ciliary persistence and unique Golgi dispersion, involving Aurora kinase A (AURKA). Our results thus indicate an association of Golgi morphology with cell cycle reentry and ciliary dynamics, underscoring the value of our profiling method in studying cellular regulation in health and disease.
    DOI:  https://doi.org/10.1083/jcb.202503083
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