bims-micesi Biomed News
on Mitotic cell signalling
Issue of 2025–04–20
seventeen papers selected by
Valentina Piano, Uniklinik Köln
  1. p31Comet Splice Variants Induce Distinct Spindle Assembly Checkpoint Dynamics due to Their Unique N-Termini.
  2. Specific mitotic events drive left-right organizer development.
  3. Single-molecule tracking reveals the dynamic turnover of Ipl1 at the kinetochores in Saccharomyces cerevisiae.
  4. Design principles for self-organization of mitotic spindle bipolarity.
  5. ANAPHASE-PROMOTING COMPLEX/CYCLOSOME coactivators maintain AURORA1 kinase homeostasis during meiotic chromosome segregation.
  6. "Mitotic" kinesin-5 is a dynamic brake for axonal growth in Drosophila.
  7. Cell cycle and age-related modulations of mouse chromosome stiffness.
  8. Meiotic spindle pushed outward by inward organelle packing.
  9. The involvement of cyclin-dependent kinase 7 (CDK7) and 9 (CDK9) in coordinating transcription and cell cycle checkpoint regulation.
  10. Glutamylation of centrosomes ensures their function by recruiting microtubule nucleation factors.
  11. Small-Molecule Mitotic Inhibitors as Anticancer Agents: Discovery, Classification, Mechanisms of Action, and Clinical Trials.
  12. Cell cycle disorders in podocytes: an emerging and increasingly recognized phenomenon.
  13. Evidence of substrate control of Cdk phosphorylation during the budding yeast cell cycle.
  14. DNA binding and mitotic phosphorylation protect polyglutamine proteins from assembly formation.
  15. PLK4 homodimerization is required for CEP152 centrosome localization and spindle organization.
  16. Enzyme-mediated proximity labeling reveals the co-translational targeting of DLGAP5 mRNA to the centrosome during mitosis.
  17. Latest News from the "Guardian": p53 Directly Activates Asymmetric Stem Cell Division Regulators.
  1. Int J Mol Sci. 2025 Mar 27. pii: 3089. [Epub ahead of print]26(7):
    p31Comet Splice Variants Induce Distinct Spindle Assembly Checkpoint Dynamics due to Their Unique N-Termini.
    Luke Scarberry, Garrett Thesing, Kevin Brennan, Madison Williams, Matthew K Summers.
      The role of p31Comet in deactivating the spindle assembly checkpoint is well described in the literature; however, the data are all completed using Variant 2 of p31Comet. p31Comet is known to be expressed as two different splice variants: Variant 1 and Variant 2. Variant 1 contains an additional 32 N-terminal residues compared to Variant 2. We report that Variant 1 exhibits a reduced ability to bind to MAD2 and thus a reduced ability to induce mitotic progression. Additionally, we show that Variant 1 exhibits reduced stability compared to Variant 2. We further show that Variant 1 is uniquely expressed in the Testes, indicating a potentially unique role of Variant 1 in that organ. Overall, we demonstrate the N-terminus of p31Comet is capable of modulating p31Comet activity in mitosis.
    Keywords:  alternative splicing; cell cycle; mitosis; spindle assembly checkpoint
    DOI:  https://doi.org/10.3390/ijms26073089
  2. Development. 2025 Apr 15. pii: dev.204687. [Epub ahead of print]
    Specific mitotic events drive left-right organizer development.
    Yan Wu, Yiling Lan, Favour Ononiwu, Abigail Poole, Kirsten Rasmussen, Jonah Da Silva, Abdalla Wael Shamil, Li-En Jao, Heidi Hehnly.
      Cell proliferation is crucial for tissue development. Here, we investigate its role in the Left-Right Organizer (LRO), which establishes the left-right (LR) axis. In zebrafish, we mapped mitotic events in Kupffer's Vesicle (KV) and identified an anteriorly enriched, FGF-dependent mitotic pattern. Laser ablation of mitotic cells and pericentrin-null mutants, both reducing mitotic events, resulted in smaller lumens, confirming that cell division is essential for KV development. Pericentrin-null mutants also exhibited defects in leftward cardiac jogging, indicative of KV dysfunction. Using a KV-specific fluorescent microtubule marker, we found that the KV rosette is a transient, centrally organized cluster interconnected by cytokinetic bridges and containing microtubule bundles. This structure emerges after the first four divisions and precedes lumen formation. Mitotic events during KV rounding coincide with rosette formation, spindle rotation, and cell extrusion, likely driven by increased packing. Eliminating the first four mitotic events disrupted rosette formation and prevented normal KV rounding. These findings demonstrate that mitotic events are critical for KV development, with cell division timing shaping KV architecture and function.
    Keywords:  Cell Patterning; Cilia; Cytokinesis; Left-Right Organizer; Lumen Formation; Microtubules; Mitosis; Rosette
    DOI:  https://doi.org/10.1242/dev.204687
  3. Life Sci Alliance. 2025 Jul;pii: e202503290. [Epub ahead of print]8(7):
    Single-molecule tracking reveals the dynamic turnover of Ipl1 at the kinetochores in Saccharomyces cerevisiae.
    Nitesh Kumar Podh, Ayan Das, Akriti Kumari, Kirti Garg, Rashmi Yadav, Kirti Kashyap, Sahil Islam, Anupam Gupta, Gunjan Mehta.
      Aurora kinase B, Ipl1 in Saccharomyces cerevisiae, is a master regulator of cell division, required for checkpoint regulation, spindle assembly and disassembly, chromosome segregation, and cytokinesis. Decades of research employed ensemble averaging methods to understand its dynamics and function; however, the dynamic information was lost because of population-based averaging. Here, we use single-molecule imaging and tracking (SMIT) to quantify the recruitment dynamics of Ipl1 at the kinetochores and spindles in live cells. Our data suggest that Ipl1 is recruited to these locations with different dynamics. We have demonstrated how the recruitment dynamics of Ipl1 at the kinetochores during metaphase changes in the presence and absence of tension across the kinetochores, in the absence of protein phosphatase 1 (Glc7), and in the absence of its known recruiters (Ctf19 and Bub1). The SMIT of other chromosome passenger complex members (Bir1, Nbl1, Sli15) suggests their hierarchical assembly at the kinetochore. Hence, SMIT provides a dynamic view of the Ipl1 trafficking at the kinetochores and spindles.
    DOI:  https://doi.org/10.26508/lsa.202503290
  4. Proc Natl Acad Sci U S A. 2025 Apr 22. 122(16): e2504470122
    Design principles for self-organization of mitotic spindle bipolarity.
    Timothy J Mitchison.
      
    DOI:  https://doi.org/10.1073/pnas.2504470122
  5. Plant Cell. 2025 Apr 17. pii: koaf089. [Epub ahead of print]
    ANAPHASE-PROMOTING COMPLEX/CYCLOSOME coactivators maintain AURORA1 kinase homeostasis during meiotic chromosome segregation.
    Jing Xu, Lian Zhou, Kaixin Chen, Runsen Huang, Baixiao Niu, Juanying Ye, Hong Ma, Gregory P Copenhaver, Yingxiang Wang.
      Faithful chromosome segregation is essential for both mitotic and meiotic cell division. The Anaphase Promoting Complex/Cyclosome (APC/C) and its coactivators are required for meiotic chromosome segregation, but their potential targets and regulatory mechanisms remain unclear in plants. Here, we performed a ubiquitinome analysis and show that Arabidopsis thaliana Aurora 1 (AUR1) is over-ubiquitinated at lysine 102 in the coactivator Cell Division Cycle 20.1 (cdc20.1) mutants and that AUR1 overexpression can partially rescue the cdc20.1 meiotic defect. We also demonstrate that APC/C ubiquitinates AUR1, leading to its degradation through the 26S proteasome pathway. Moreover, the APC/C subunit and coactivators Cell Cycle Switch 52 A2/B (CCS52A2/B) and CDC20.1 interact with AUR1 both in vitro and in vivo. Intriguingly, CCS52A2/B promotes AUR1 ubiquitination and degradation, while CDC20.1 prevents AUR1 degradation. Consistent with this finding, AUR1 levels are lower in cdc20.1 and higher in ccs52 mutants relative to Col-0, and mutation of CCS52A2/B causes defects in meiotic spindle assembly and homologous chromosome segregation. Genetic analyses demonstrate that Arabidopsis Anaphase-Promoting Complex/Cyclosome subunit 8 (APC8), CDC20.1, CCS52 and AUR1 act in the same pathway to control meiotic spindle assembly and homologous chromosome segregation. Thus, this work provides mechanistic insight into the role of APC/C coactivators in regulating AUR1 homeostasis during meiosis in plants.
    Keywords:  Anaphase-Promoting Complex/Cyclosome; Aurora kinase; Chromosome segregation; Meiosis; Ubiquitination
    DOI:  https://doi.org/10.1093/plcell/koaf089
  6. Development. 2025 Apr 14. pii: dev.204424. [Epub ahead of print]
    "Mitotic" kinesin-5 is a dynamic brake for axonal growth in Drosophila.
    Wen Lu, Brad S Lee, Helen Xue Ying Deng, Margot Lakonishok, Enrique Martin-Blanco, Vladimir I Gelfand.
      During neuronal development, microtubule reorganization shapes axons and dendrites, establishing the framework for efficient nervous system wiring. Our previous work demonstrated the role of kinesin-1 in driving microtubule sliding, which powers early axon outgrowth and regeneration in Drosophila melanogaster. Here, we reveal a critical new role of kinesin-5, a mitotic motor, in modulating postmitotic neuron development. The Drosophila kinesin-5, Klp61F, is expressed in larval brain neurons, with high levels in ventral nerve cord (VNC) neurons. Knockdown of Klp61F in neurons leads to severe adult locomotion defects and lethality, primarily due to defects in VNC motor neurons. Klp61F depletion results in excessive microtubule penetration into the axon growth cone, causing significant axon growth defects in culture and in vivo. These defects are rescued by a chimeric human-Drosophila kinesin-5 motor, indicating a conserved role of kinesin-5 in neuronal development. Altogether, we propose that kinesin-5 acts as a brake on kinesin-1-driven microtubule sliding, ensuring proper axon pathfinding in growing neurons.
    Keywords:  Axonal growth; Kinesin-5; Microtubules; Mitotic motor; Motor neurons; Neuronal development
    DOI:  https://doi.org/10.1242/dev.204424
  7. Elife. 2025 Apr 14. pii: RP97403. [Epub ahead of print]13
    Cell cycle and age-related modulations of mouse chromosome stiffness.
    Ning Liu, Wenan Qiang, Philip W Jordan, John F Marko, Huanyu Qiao.
      Chromosome structure is complex, and many aspects of chromosome organization are still not understood. Measuring the stiffness of chromosomes offers valuable insight into their structural properties. In this study, we analyzed the stiffness of chromosomes from metaphase I (MI) and metaphase II (MII) oocytes. Our results revealed a tenfold increase in stiffness (Young's modulus) of MI chromosomes compared to somatic chromosomes. Furthermore, the stiffness of MII chromosomes was found to be lower than that of MI chromosomes. We examined the role of meiosis-specific cohesin complexes in regulating chromosome stiffness. Surprisingly, the stiffness of chromosomes from three meiosis-specific cohesin mutants did not significantly differ from that of wild-type chromosomes, indicating that these cohesins may not be primary determinants of chromosome stiffness. Additionally, our findings revealed an age-related increase of chromosome stiffness for MI oocytes. Since aging is associated with elevated levels of DNA damage, we investigated the impact of etoposide-induced DNA damage on chromosome stiffness and found that it led to a reduction in stiffness in MI oocytes. Overall, our study underscores the dynamic and cyclical nature of chromosome stiffness, modulated by both the cell cycle and age-related factors.
    Keywords:  age; chromosome stiffness; cohesin protein; meiosis; mouse; oocyte; physics of living systems; spermatocyte
    DOI:  https://doi.org/10.7554/eLife.97403
  8. Trends Cell Biol. 2025 Apr 10. pii: S0962-8924(25)00086-8. [Epub ahead of print]
    Meiotic spindle pushed outward by inward organelle packing.
    Xin Xiang.
      In Caenorhabditis elegans oocytes, meiotic spindle movement toward the cortex before anaphase depends on kinesin-1. A recent study by Aquino et al. uncovers a novel mechanism whereby the inward organelle packing driven by kinesin-1 excludes the spindle from the center, thereby causing it to be positioned near the cortex.
    Keywords:  C. elegans oocyte; kinesin-1; microtubule polarity; organelle movement; spindle positioning; volume exclusion
    DOI:  https://doi.org/10.1016/j.tcb.2025.03.006
  9. Cell Cycle. 2025 Apr 14. 1-13
    The involvement of cyclin-dependent kinase 7 (CDK7) and 9 (CDK9) in coordinating transcription and cell cycle checkpoint regulation.
    Cheng-Fan Lee, Kenneth J Pienta, Sarah R Amend.
      Cells regulate the expression of cell cycle-related genes, including cyclins essential for mitosis, through the transcriptional activity of the positive transcription elongation factor b (P-TEFb), a complex comprising CDK9, cyclin T, and transcription factors. P-TEFb cooperates with CDK7 to activate RNA polymerase. In response to DNA stress, the cell cycle shifts from mitosis to repair, triggering cell cycle arrest and the activation of DNA repair genes. This tight coordination between transcription, cell cycle progression, and DNA stress response is crucial for maintaining cellular integrity. Cyclin-dependent kinases CDK7 and CDK9 are central to both transcription and cell cycle regulation. CDK7 functions as the CDK-activating kinase (CAK), essential for activating other CDKs, while CDK9 acts as a critical integrator of signals from both the cell cycle and transcriptional machinery. This review elucidates the mechanisms by which CDK7 and CDK9 regulate the mitotic process and cell cycle checkpoints, emphasizing their roles in balancing cell growth, homeostasis, and DNA repair through transcriptional control.
    Keywords:  CDK7; CDK9; Cell cycle; transcription
    DOI:  https://doi.org/10.1080/15384101.2025.2485844
  10. EMBO J. 2025 Apr 14.
    Glutamylation of centrosomes ensures their function by recruiting microtubule nucleation factors.
    Shi-Rong Hong, Yi-Chien Chuang, Wen-Ting Yang, Chiou-Shian Song, Hung-Wei Yeh, Bing-Huan Wu, I-Hsuan Lin, Po-Chun Chou, Shiau-Chi Chen, Lohitaksh Sharma, Jui-Chen Lu, Rou-Ying Li, Ya-Chu Chang, Kuan-Ju Liao, Hui-Chun Cheng, Won-Jing Wang, Lily Hui-Ching Wang, Yu-Chun Lin.
      Centrosomes are tubulin-based organelles that undergo glutamylation, a post-translational modification that conjugates glutamic acid residues to tubulins. Although centrosomal glutamylation has been known for several decades, how this modification regulates centrosome structure and function remains unclear. To address this long-standing issue, we developed a method to spatiotemporally reduce centrosomal glutamylation by recruiting an engineered deglutamylase to centrosomes. We found that centrosome structure remains largely unaffected by centrosomal hypoglutamylation. Intriguingly, glutamylation physically recruits, via electrostatic forces, the NEDD1/CEP192/γ-tubulin complex to centrosomes, ensuring microtubule nucleation and proper trafficking of centriolar satellites. The consequent defect in centriolar satellite trafficking leads to reduced levels of the ciliogenesis factor Talpid3, suppressing ciliogenesis. Centrosome glutamylation also promotes proper mitotic spindle formation and mitosis. In summary, our study provides a new approach to spatiotemporally manipulate glutamylation at centrosomes, and offers novel insights into how centrosomes are organized and regulated by glutamylation.
    Keywords:  Centriolar satellites; Centrosomes; Glutamylation; Microtubules; Primary Cilia
    DOI:  https://doi.org/10.1038/s44318-025-00435-y
  11. Int J Mol Sci. 2025 Apr 01. pii: 3279. [Epub ahead of print]26(7):
    Small-Molecule Mitotic Inhibitors as Anticancer Agents: Discovery, Classification, Mechanisms of Action, and Clinical Trials.
    Yazmin Salinas, Subhash C Chauhan, Debasish Bandyopadhyay.
      Despite decades of research, cancer continues to be a disease of great concern to millions of people around the world. It has been responsible for a total of 609,820 deaths in the U.S. alone in 2023. Over the years, many drugs have been developed to remove or reduce the disease's impact, all with varying mechanisms of action and side effects. One class of these drugs is small-molecule mitotic inhibitors. These drugs inhibit cancer cell mitosis or self-replication, impeding cell proliferation and eventually leading to cell death. In this paper, small-molecule mitotic inhibitors are discussed and classified through their discovery, underlying chemistry, and mechanism(s) of action. The binding/inhibition of microtubule-related proteins, DNA damage through the inhibition of Checkpoint Kinase 1 protein, and the inhibition of mitotic kinase proteins are discussed in terms of their anticancer activity to provide an overview of a variety of mitotic inhibitors currently commercially available or under investigation, including those in ongoing clinical trial. Clinical trials for anti-mitotic agents are discussed to track research progress, gauge current understanding, and identify possible future prospects. Additionally, antibody-drug conjugates that use mitotic inhibitors as cytotoxic payloads are discussed as possible ways of administering effective anticancer treatments with minimal toxicity.
    Keywords:  antibody–drug conjugates; anticancer agent; clinical trials; cytotoxic; kinase proteins; microtubule-associated proteins; mitosis; mitotic proteins; small-molecule inhibitors; taxanes
    DOI:  https://doi.org/10.3390/ijms26073279
  12. Cell Death Discov. 2025 Apr 17. 11(1): 182
    Cell cycle disorders in podocytes: an emerging and increasingly recognized phenomenon.
    Chaojie Zhang, Jia Guo.
      Proteinuria is observed in various kidney diseases and is frequently associated with a compromised glomerular filtration barrier. Podocytes, as a crucial component of this barrier, play an essential role in preserving the kidney's normal filtration function. Podocytes are terminally differentiated cells that typically do not proliferate. However, certain harmful stimuli can trigger podocytes to re-enter the cell cycle. Due to its unique cytoskeletal structure, podocytes are unable to maintain the structure of the foot process and complete cell division at the same time, eventually form binucleated or multinucleated podocytes. Studies have found that podocytes re-entering the cell cycle are more susceptible to injury, and are prone to detachment from the basement membrane or apoptosis, which are accompanied by the widening of foot processes. This eventually leads to podocyte mitotic catastrophe and the development of proteinuria. Podocyte cell cycle disorders have previously been found mainly in focal segmental glomerulosclerosis and IgA nephropathy. In recent years, this phenomenon has been frequently identified in diabetic kidney disease and lupus nephritis. An expanding body of research has begun to investigate the mechanisms underlying podocyte cell cycle disorders, including cell cycle re-entry, cell cycle arrest, and mitotic catastrophe. This review consolidates the existing literature on podocyte cell cycle disorders in renal diseases and summarizes the molecules that trigger podocyte re-entry into the cell cycle, thereby providing new drug targets for mitigating podocyte damage. This is essential for alleviating podocyte injury, reducing proteinuria, and delaying the progression of kidney diseases.
    DOI:  https://doi.org/10.1038/s41420-025-02486-w
  13. Cell Rep. 2025 Apr 11. pii: S2211-1247(25)00305-5. [Epub ahead of print]44(4): 115534
    Evidence of substrate control of Cdk phosphorylation during the budding yeast cell cycle.
    Luca Takacs, Lina Gerontogianni, Kimberly Quililan, Helen Flynn, Frank Uhlmann.
      A series of sequential events orchestrates cell growth and division, set in motion by cyclin-dependent kinases (Cdks). In the "qualitative model" for Cdk control, order is achieved by cell cycle stage-specific cyclins. However, single-cyclin cells retain cell cycle order. In an alternative "quantitative model," increasing Cdk activity triggers substrate phosphorylation at sequential thresholds. Here, we test a key prediction from the quantitative model: the best Cdk substrates should be the first to be phosphorylated. Phosphoproteome analysis of synchronous budding yeast cultures, against expectations, reveals little correlation between known in vitro Cdk phosphorylation rates and observed in vivo phosphorylation timing. Incorporating Cdk-counteracting phosphatases that impose phosphorylation thresholds does not improve the correlation. Instead of kinase-phosphatase control (i.e., "regulator control"), our phosphoproteome patterns reveal signatures of "substrate control," including substrate-defined phosphorylation waves. The changing behavior of the substrates themselves therefore contributes to ordering their Cdk phosphorylation during the budding yeast cell cycle.
    Keywords:  CP: Cell biology; CP: Molecular biology; S. cerevisiae; cell cycle; cyclin-dependent kinase, Cdk; phosphatases; phosphoproteomics; qualitative Cdk control; quantitative Cdk control; substrate control
    DOI:  https://doi.org/10.1016/j.celrep.2025.115534
  14. Cell. 2025 Apr 12. pii: S0092-8674(25)00349-6. [Epub ahead of print]
    DNA binding and mitotic phosphorylation protect polyglutamine proteins from assembly formation.
    Shady Saad, Tomek Swigut, Saman Tabatabaee, Pranav Lalgudi, Daniel F Jarosz, Joanna Wysocka.
      Polyglutamine (polyQ) expansion is associated with pathogenic protein aggregation in neurodegenerative disorders. However, long polyQ tracts are also found in many transcription factors (TFs), such as FOXP2, a TF implicated in human speech. Here, we explore how FOXP2 and other glutamine-rich TFs avoid unscheduled assembly. Throughout interphase, DNA binding, irrespective of sequence specificity, has a solubilizing effect. During mitosis, multiple phosphorylation events promote FOXP2's eviction from chromatin and supplant the solubilizing function of DNA. Further, human-specific amino acid substitutions linked to the evolution of speech map to a mitotic phospho-patch, the "EVO patch," and reduce the propensity of the human FOXP2 to assemble. Fusing the pathogenic form of Huntingtin to either a DNA-binding domain, a phosphomimetic variant of this EVO patch, or a negatively charged peptide is sufficient to diminish assembly formation, suggesting that hijacking mechanisms governing solubility of glutamine-rich TFs may offer new strategies for treatment of polyQ expansion diseases.
    Keywords:  FOXP2; Huntington's disease; amyloid; evolution; glutamine-rich proteins; human speech; language; polyglutamine; protein assemblies; transcription factors
    DOI:  https://doi.org/10.1016/j.cell.2025.03.031
  15. J Mol Biol. 2025 Apr 11. pii: S0022-2836(25)00218-9. [Epub ahead of print] 169152
    PLK4 homodimerization is required for CEP152 centrosome localization and spindle organization.
    Harshita Kasera, Srishti Sanghi, Priyanka Singh.
      The centrosome-specific Polo-Like Kinase 4 (PLK4) is a unique serine/threonine kinase family member that homodimerizes using its cryptic polo-box (CPB) region. PLK4 homodimerization causes transphosphorylation, which activates its ubiquitin-mediated degradation. The same CPB interacts with upstream centrosome recruiters, CEP152 and CEP192 in human cells. However, the involvement of PLK4 homodimerization with the CEP192-CEP152 network remains unexplored. This work identified a cancerous PLK4 variant, which truncated the protein to disrupt the CPB at 774 residue. The truncated PLK4 is unable to homodimerize or interact with CEP152 or CEP192. During the S-phase, CEP152 recruits PLK4 to centrosomes, and the homodimerization of PLK4 is needed to maintain CEP152 at centrosomes. The reduction in levels of CEP152 on PLK4 homodimerization mutant expression correlates to pericentrin at S-phase centrosomes, which causes unfocussed spindles at the M-phase and reduces cell viability. The work shows a cross-dependency between CEP152 and PLK4 homodimerization for centrosome functioning, which is disrupted in cancer.
    Keywords:  CEP152; CEP192; Centriole; Centrosome; PLK4
    DOI:  https://doi.org/10.1016/j.jmb.2025.169152
  16. RSC Chem Biol. 2025 Mar 26.
    Enzyme-mediated proximity labeling reveals the co-translational targeting of DLGAP5 mRNA to the centrosome during mitosis.
    Gang Wang, Mo Li, Peng Zou.
      Subcellular RNA localization is a conserved mechanism in eukaryotic cells and plays critical roles in diverse physiological processes including cell proliferation, differentiation, and embryo development. Nevertheless, the characterization of centrosome-localized mRNAs remains underexplored due to technical difficulties. In this study, we utilize APEX2-mediated proximity labeling to map the centrosome-proximal transcriptome, identifying DLGAP5 mRNA as a novel centrosome-localized transcript during mitosis. Using a combination of drug perturbation, truncation, deletion, and mutagenesis, we demonstrate that microtubule binding of nascent MBD1 polypeptides is required for centrosomal transport of DLGAP5 mRNA. Our data also reveal that mRNA targeting efficiency is tightly linked to the coding sequence (CDS) length. Thus, our study provides a transcriptomic resource for future investigation of centrosome-localized RNAs and sheds light on mechanisms underlying mRNA centrosomal localization.
    DOI:  https://doi.org/10.1039/d4cb00155a
  17. Int J Mol Sci. 2025 Mar 29. pii: 3171. [Epub ahead of print]26(7):
    Latest News from the "Guardian": p53 Directly Activates Asymmetric Stem Cell Division Regulators.
    Ana Carmena.
      Since its discovery in 1979, the human tumor suppressor gene TP53-also known as the "guardian of the genome"-has been the subject of intense research. Mutated in most human cancers, TP53 has traditionally been considered a key fighter against stress factors by trans-activating a network of target genes that promote cell cycle arrest, DNA repair, or apoptosis. Intriguingly, over the past years, novel non-canonical functions of p53 in unstressed cells have also emerged, including the mode of stem cell division regulation. However, the mechanisms by which p53 modulates these novel functions remain incompletely understood. In a recent work, we found that Drosophila p53 controls asymmetric stem cell division (ASCD) in neural stem cells by transcriptionally activating core ASCD regulators, such as the conserved cell-fate determinants Numb and Brat (NUMB and TRIM3/TRIM2/TRIM32 in humans, respectively). In this short communication, we comment on this new finding, the mild phenotypes associated with Drosophila p53 mutants in this context, as well as novel avenues for future research.
    Keywords:  Brat/TRIM proteins; Drosophila; Numb/NUMB; Traf4/TRAF4; asymmetric stem cell division; neural stem cells; p53
    DOI:  https://doi.org/10.3390/ijms26073171
This page is being maintained by Thomas Krichel. It was last updated on 2025‒05‒11 at 14:58.