bims-micesi Biomed News
on Mitotic cell signalling
Issue of 2023‒12‒10
six papers selected by
Valentina Piano, Uniklinik Köln
  1. NAK-associated protein 1/NAP1 activates TBK1 to ensure accurate mitosis and cytokinesis.
  2. Cell cycle control by cell-matrix interactions.
  3. CRMP5 participates in oocyte meiosis by regulating spastin to correct microtubule-kinetochore misconnection.
  4. The doublecortin-family kinase ZYG-8 DCLK1 regulates motor activity to achieve proper force balance in C. elegans acentrosomal spindles.
  5. Downregulation of BUBR1 regulates the proliferation and cell cycle of breast cancer cells and increases the sensitivity of cells to cisplatin.
  6. Phosphatase to kinase switch of a critical enzyme contributes to timing of cell differentiation.
  1. J Cell Biol. 2024 Feb 05. pii: e202303082. [Epub ahead of print]223(2):
    NAK-associated protein 1/NAP1 activates TBK1 to ensure accurate mitosis and cytokinesis.
    Swagatika Paul, Shireen A Sarraf, Ki Hong Nam, Leila Zavar, Nicole DeFoor, Sahitya Ranjan Biswas, Lauren E Fritsch, Tomer M Yaron, Jared L Johnson, Emily M Huntsman, Lewis C Cantley, Alban Ordureau, Alicia M Pickrell.
      Subcellular location and activation of Tank Binding Kinase 1 (TBK1) govern precise progression through mitosis. Either loss of activated TBK1 or its sequestration from the centrosomes causes errors in mitosis and growth defects. Yet, what regulates its recruitment and activation on the centrosomes is unknown. We identified that NAK-associated protein 1 (NAP1) is essential for mitosis, binding to and activating TBK1, which both localize to centrosomes. Loss of NAP1 causes several mitotic and cytokinetic defects due to inactivation of TBK1. Our quantitative phosphoproteomics identified numerous TBK1 substrates that are not only confined to the centrosomes but are also associated with microtubules. Substrate motifs analysis indicates that TBK1 acts upstream of other essential cell cycle kinases like Aurora and PAK kinases. We also identified NAP1 as a TBK1 substrate phosphorylating NAP1 at S318 to promote its degradation by the ubiquitin proteasomal system. These data uncover an important distinct function for the NAP1-TBK1 complex during cell division.
    DOI:  https://doi.org/10.1083/jcb.202303082
  2. Curr Opin Cell Biol. 2023 Dec 05. pii: S0955-0674(23)00137-0. [Epub ahead of print]86 102288
    Cell cycle control by cell-matrix interactions.
    Michael J Jones, Matthew C Jones.
      Cell adhesion to the extracellular matrix (ECM) is required for normal cell cycle progression and accurate cell division. However, how cell adhesion to the wide range of ECM proteins found in human tissues influences the cell cycle is not fully understood. The composition and physical properties of the ECM can have profound effects on cell proliferation but can also promote cell cycle exit and quiescence. Furthermore, during tumor development and progression, changes in the ECM can drive both cancer cell proliferation and dormancy. Cell-matrix adhesion is primarily sensed via integrin-associated adhesion complexes, which in turn are regulated by the cell cycle machinery. In particular, cyclin-dependent kinase 1 (CDK1) has been shown to play a crucial role in regulating adhesion complexes during interphase and entry into mitosis. These reciprocal links between cell cycle progression and cell-matrix interactions are now being identified.
    DOI:  https://doi.org/10.1016/j.ceb.2023.102288
  3. Zygote. 2023 Dec 04. 1-7
    CRMP5 participates in oocyte meiosis by regulating spastin to correct microtubule-kinetochore misconnection.
    Zhen Jin, Zhi-Cai Zhang, Chen-Yu Xiao, Mei-Qi Li, Qian-Ru Li, Lei-Lei Gao.
      Our previous studies have suggested that spastin, which aggregates on spindle microtubules in oocytes, may promote the assembly of mouse oocyte spindles by cutting microtubules. This action may be related to CRMP5, as knocking down CRMP5 results in reduced spindle microtubule density and maturation defects in oocytes. In this study, we found that, after knocking down CRMP5 in oocytes, spastin distribution shifted from the spindle to the spindle poles and errors in microtubule-kinetochore attachment appeared in oocyte spindles. However, CRMP5 did not interact with the other two microtubule-severing proteins, katanin-like-1 (KATNAL1) and fidgetin-like-1 (FIGNL1), which aggregate at the spindle poles. We speculate that, in oocytes, due to the reduction of spastin distribution on chromosomes after knocking down CRMP5, microtubule-kinetochore errors cannot be corrected through severing, resulting in meiotic division abnormalities and maturation defects in oocytes. This finding provides new insights into the regulatory mechanisms of spastin in oocytes and important opportunities for the study of meiotic division mechanisms.
    DOI:  https://doi.org/10.1017/S0967199423000564
  4. bioRxiv. 2023 Nov 22. pii: 2023.11.22.568242. [Epub ahead of print]
    The doublecortin-family kinase ZYG-8 DCLK1 regulates motor activity to achieve proper force balance in C. elegans acentrosomal spindles.
    Emily R Czajkowski, Nikita S Divekar, Sarah M Wignall.
      Although centrosomes help organize spindles in most cell types, oocytes of most species lack these structures. During acentrosomal spindle assembly in C. elegans oocytes, microtubule minus ends are sorted outwards away from the chromosomes where they form poles, but then these outward forces must be balanced to form a stable bipolar structure. How proper force balance is achieved in these spindles is not known. Here, we have gained insight into this question through studies of ZYG-8, a conserved doublecortin-family kinase; the mammalian homolog of this microtubule-associated protein is upregulated in many cancers and has been implicated in cell division, but the mechanisms by which it functions are poorly understood. Interestingly, we found that ZYG-8 depletion from oocytes resulted in spindles that were over-elongated, suggesting that there was excess outward force following ZYG-8 removal. Experiments with monopolar spindles confirmed this hypothesis and revealed a role for ZYG-8 in regulating the force-generating motor BMK-1/kinesin-5. Importantly, further investigation revealed that kinase activity is required for the function of ZYG-8 in both meiosis and mitosis. Altogether, our results support a model in which ZYG-8 regulates motor-driven forces within the oocyte spindle, thus identifying a new function for a doublecortin-family protein in cell division.
    DOI:  https://doi.org/10.1101/2023.11.22.568242
  5. In Vitro Cell Dev Biol Anim. 2023 Dec 04.
    Downregulation of BUBR1 regulates the proliferation and cell cycle of breast cancer cells and increases the sensitivity of cells to cisplatin.
    Yiran Lu, Ruiqing Wang, Song He, Qing Zhang, Jiahui Wei, Jinping Hu, Yu Ding.
      Breast cancer (BC) is a significant tissue for women's health worldwide. The spindle assembly checkpoint protein family includes BUBR1 (Bub1-related kinase or MAD3/Bub1b). High expression of BUBR1 promotes cell cycle disorders, leading to cell carcinogenesis and cancer progression. However, the underlying molecular mechanism and the role of BUBR1 in BC progression are unclear. The published dataset was analyzed to evaluate the clinical relevance of BUBR1. BUBR1 was knocked down in BC cells using shRNA. The CCK-8 assay was used to measure the cell viability, and mRNA and protein expression levels were detected by RT-qPCR and Western blot (WB). Cell apoptosis and cell cycle were detected by flow cytometry. Subcutaneous xenograft model was used to assess in vivo tumor growth. BUBR1 was found to be highly expressed in BC. The high expression of BUBR1 was associated with poor prognosis of BC patients. Upon BUBR1 knockdown using shRNA, the proliferation and metastatic ability of cells were decreased. Moreover, the cells with BUBR1 knockdown underwent cell cycle arrest. And the results showed that BUBR1 loss inhibited the phosphorylation of TAK1/JNK. In vitro and in vivo studies indicated the knockdown of BUBR1 rendered the BC cells more sensitive to cisplatin. In summary, BUBR1 may be a potential therapeutic target for BC and targeting BUBR1 may help overcome cisplatin resistance in BC patients.
    Keywords:  BUBR1; Breast cancer; Cell cycle; Cisplatin sensitivity; TAK1/JNK
    DOI:  https://doi.org/10.1007/s11626-023-00823-w
  6. mBio. 2023 Dec 06. e0212523
    Phosphatase to kinase switch of a critical enzyme contributes to timing of cell differentiation.
    Trisha N Chong, Mayura Panjalingam, Saumya Saurabh, Lucy Shapiro.
      IMPORTANCE: The process of cell differentiation is highly regulated in both prokaryotic and eukaryotic organisms. The aquatic bacterium, Caulobacter crescentus, undergoes programmed cell differentiation from a motile swarmer cell to a stationary stalked cell with each cell cycle. This critical event is regulated at multiple levels. Kinase activity of the bifunctional enzyme, PleC, is limited to a brief period when it initiates the molecular signaling cascade that results in cell differentiation. Conversely, PleC phosphatase activity is required for pili formation and flagellar rotation. We show that PleC is localized to the flagellar pole by the scaffold protein, PodJ, which is known to suppress PleC kinase activity in vitro. PleC mutants that are unable to bind PodJ have increased kinase activity in vivo, resulting in premature differentiation. We propose a model in which PodJ regulation of PleC's enzymatic activity contributes to the robust timing of cell differentiation during the Caulobacter cell cycle.
    Keywords:  Caulobacter; PAS domain; cell differentiation; histidine kinase; phosphatase; two-component systems
    DOI:  https://doi.org/10.1128/mbio.02125-23
This page is being maintained by Thomas Krichel. It was last updated on 2024‒03‒10 at 9:26.