Faculty Opinions recommendation of hNuf2 inhibition blocks stable kinetochore-microtubule attachment and induces mitotic cell death in HeLa cells.

2002 ◽  
Author(s):  
Duane Compton
Keyword(s):  
Cell Death ◽  
Hela Cells ◽  
Mitotic Cell ◽  
Microtubule Attachment

scholarly journals hNuf2 inhibition blocks stable kinetochore–microtubule attachment and induces mitotic cell death in HeLa cells

2002 ◽  
Vol 159 (4) ◽  
pp. 549-555 ◽  
Author(s):  
Jennifer G. DeLuca ◽  
Ben Moree ◽  
Jennifer M. Hickey ◽  
John V. Kilmartin ◽  
E.D. Salmon
Keyword(s):  
Cell Death ◽  
Hela Cells ◽  
Spindle Checkpoint ◽  
Attachment Site ◽  
Mitotic Cell ◽  
Cytoplasmic Dynein ◽  
Microtubule Attachment ◽  
Microtubule Motors ◽  
Spindle Microtubules ◽  
Cell Cycle Block

Identification of proteins that couple kinetochores to spindle microtubules is critical for understanding how accurate chromosome segregation is achieved in mitosis. Here we show that the protein hNuf2 specifically functions at kinetochores for stable microtubule attachment in HeLa cells. When hNuf2 is depleted by RNA interference, spindle formation occurs normally as cells enter mitosis, but kinetochores fail to form their attachments to spindle microtubules and cells block in prometaphase with an active spindle checkpoint. Kinetochores depleted of hNuf2 retain the microtubule motors CENP-E and cytoplasmic dynein, proteins previously implicated in recruiting kinetochore microtubules. Kinetochores also retain detectable levels of the spindle checkpoint proteins Mad2 and BubR1, as expected for activation of the spindle checkpoint by unattached kinetochores. In addition, the cell cycle block produced by hNuf2 depletion induces mitotic cells to undergo cell death. These data highlight a specific role for hNuf2 in kinetochore–microtubule attachment and suggest that hNuf2 is part of a molecular linker between the kinetochore attachment site and tubulin subunits within the lattice of attached plus ends.

scholarly journals Inhibitors of Phosphatidylinositol 3′-Kinases Promote Mitotic Cell Death in HeLa Cells

PLoS ONE ◽  
2012 ◽  
Vol 7 (4) ◽  
pp. e35665 ◽  
Author(s):  
Heli Hou ◽  
Yingyin Zhang ◽  
Yun Huang ◽  
Qiyi Yi ◽  
Lei Lv ◽  
...  
Keyword(s):  
Cell Death ◽  
Hela Cells ◽  
Mitotic Cell ◽  
Phosphatidylinositol 3

scholarly journals RhoB controls the 24 kDa FGF-2-induced radioresistance in HeLa cells by preventing post-mitotic cell death

Oncogene ◽  
2002 ◽  
Vol 21 (39) ◽  
pp. 5998-6006 ◽  
Author(s):  
Isabelle Ader ◽  
Christine Toulas ◽  
Florence Dalenc ◽  
Caroline Delmas ◽  
Jacques Bonnet ◽  
...  
Keyword(s):  
Cell Death ◽  
Hela Cells ◽  
Mitotic Cell

scholarly journals The STING1 network regulates autophagy and cell death

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Ruoxi Zhang ◽  
Rui Kang ◽  
Daolin Tang
Keyword(s):  
Cell Death ◽  
Mitotic Cell ◽  
Therapeutic Interventions ◽  
Type I Interferons ◽  
Microbial Pathogens ◽  
Type I ◽  
Autophagic Degradation ◽  
Health And Disease ◽  
Shed Light ◽  
Pro Inflammatory Cytokines

AbstractCell death and immune response are at the core of life. In past decades, the endoplasmic reticulum (ER) protein STING1 (also known as STING or TMEM173) was found to play a fundamental role in the production of type I interferons (IFNs) and pro-inflammatory cytokines in response to DNA derived from invading microbial pathogens or damaged hosts by activating multiple transcription factors. In addition to this well-known function in infection, inflammation, and immunity, emerging evidence suggests that the STING1-dependent signaling network is implicated in health and disease by regulating autophagic degradation or various cell death modalities (e.g., apoptosis, necroptosis, pyroptosis, ferroptosis, mitotic cell death, and immunogenic cell death [ICD]). Here, we outline the latest advances in our understanding of the regulating mechanisms and signaling pathways of STING1 in autophagy and cell death, which may shed light on new targets for therapeutic interventions.

scholarly journals Enhance the Immune Checkpoint Inhibitors Efficacy with Radiotherapy Induced Immunogenic Cell Death: A Comprehensive Review and Latest Developments

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 678 ◽  
Author(s):  
Adrien Procureur ◽  
Audrey Simonaggio ◽  
Jean-Emmanuel Bibault ◽  
Stéphane Oudard ◽  
Yann-Alexandre Vano
Keyword(s):  
Cell Death ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Tumor Antigens ◽  
Checkpoint Inhibitors ◽  
Mitotic Cell ◽  
Immunogenic Cell Death ◽  
Dna Damages ◽  
Multiple Tumor ◽  
Tumor Types

The immunogenic cell death (ICD) is defined as a regulated cell death able to induce an adaptive immunity. It depends on different parameters including sufficient antigenicity, adjuvanticity and favorable microenvironment conditions. Radiation therapy (RT), a pillar of modern cancer treatment, is being used in many tumor types in curative, (neo) adjuvant, as well as metastatic settings. The anti-tumor effects of RT have been traditionally attributed to the mitotic cell death resulting from the DNA damages triggered by the release of reactive oxygen species. Recent evidence suggests that RT may also exert its anti-tumor effect by recruiting tumor-specific immunity. RT is able to induce the release of tumor antigens, to act as an immune adjuvant and thus to synergize with the anti-tumor immunity. The advent of new efficient immunotherapeutic agents, such as immune checkpoint inhibitors (ICI), in multiple tumor types sheds new light on the opportunity of combining RT and ICI. Here, we will describe the biological and radiobiological rationale of the RT-induced ICD. We will then focus on the interest to combine RT and ICI, from bench to bedside, and summarize the clinical data existing with this combination. Finally, RT technical adaptations to optimize the ICD induction will be discussed.

Comparative Proteomic Analysis of Indioside D-Triggered Cell Death in HeLa Cells

2008 ◽  
Vol 7 (5) ◽  
pp. 2050-2058 ◽  
Author(s):  
Chi Chun Wong ◽  
Ying Wang ◽  
Ka-Wing Cheng ◽  
Jen-Fu Chiu ◽  
Qing-Yu He ◽  
...  
Keyword(s):  
Cell Death ◽  
Hela Cells ◽  
Proteomic Analysis ◽  
Comparative Proteomic Analysis

scholarly journals Consequences of mitotic slippage for antimicrotubule drug therapy

2017 ◽  
Vol 24 (9) ◽  
pp. T97-T106 ◽  
Author(s):  
Bing Cheng ◽  
Karen Crasta
Keyword(s):  
Cell Death ◽  
Spindle Assembly Checkpoint ◽  
Mitotic Cell ◽  
G1 Arrest ◽  
Front Line ◽  
Cell Fates ◽  
Mitotic Slippage ◽  
Drug Treatment Outcomes ◽  
Antimicrotubule Agents ◽  
Sustained Activation

Antimicrotubule agents are commonly utilised as front-line therapies against several malignancies, either by themselves or as combination therapies. Cell-based studies have pinpointed the anti-proliferative basis of action to be a consequence of perturbation of microtubule dynamics leading to sustained activation of the spindle assembly checkpoint, prolonged mitotic arrest and mitotic cell death. However, depending on the biological context and cell type, cells may take an alternative route besides mitotic cell death via a process known as mitotic slippage. Here, mitotically arrested cells ‘slip’ to the next interphase without undergoing proper chromosome segregation and cytokinesis. These post-slippage cells in turn have two main cell fates, either cell death or a G1 arrest ensuing in senescence. In this review, we take a look at the factors determining mitotic cell death vs mitotic slippage, post-slippage cell fates and accompanying features, and their consequences for antimicrotubule drug treatment outcomes.

scholarly journals BUB1 mediation of caspase-independent mitotic death determines cell fate

2007 ◽  
Vol 178 (2) ◽  
pp. 283-296 ◽  
Author(s):  
Yohei Niikura ◽  
Amruta Dixit ◽  
Ray Scott ◽  
Guy Perkins ◽  
Katsumi Kitagawa
Keyword(s):  
Cell Death ◽  
Cell Fate ◽  
Cell Lines ◽  
Chromosome Instability ◽  
Spindle Checkpoint ◽  
Mitotic Cell ◽  
Endonuclease G ◽  
Colon Tumors ◽  
Mitotic Death ◽  
Apoptosis Inducing Factor

The spindle checkpoint that monitors kinetochore–microtubule attachment has been implicated in tumorigenesis; however, the relation between the spindle checkpoint and cell death remains obscure. In BUB1-deficient (but not MAD2-deficient) cells, conditions that activate the spindle checkpoint (i.e., cold shock or treatment with nocodazole, paclitaxel, or 17-AAG) induced DNA fragmentation during early mitosis. This mitotic cell death was independent of caspase activation; therefore, we named it caspase-independent mitotic death (CIMD). CIMD depends on p73, a homologue of p53, but not on p53. CIMD also depends on apoptosis-inducing factor and endonuclease G, which are effectors of caspase-independent cell death. Treatment with nocodazole, paclitaxel, or 17-AAG induced CIMD in cell lines derived from colon tumors with chromosome instability, but not in cells from colon tumors with microsatellite instability. This result was due to low BUB1 expression in the former cell lines. When BUB1 is completely depleted, aneuploidy rather than CIMD occurs. These results suggest that cells prone to substantial chromosome missegregation might be eliminated via CIMD.

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