Imbalance of the spindle-assembly checkpoint promotes spindle poison-mediated cytotoxicity with distinct kinetics.

Abstract:

:Disrupting microtubule dynamics with spindle poisons activates the spindle-assembly checkpoint (SAC) and induces mitotic cell death. However, mitotic exit can occur prematurely without proper chromosomal segregation or cytokinesis by a process termed mitotic slippage. It remains controversial whether mitotic slippage increases the cytotoxicity of spindle poisons or the converse. Altering the SAC induces either mitotic cell death or mitotic slippage. While knockout of MAD2-binding protein p31comet strengthened the SAC and promoted mitotic cell death, knockout of TRIP13 had the opposite effect of triggering mitotic slippage. We demonstrated that mitotic slippage prevented mitotic cell death caused by spindle poisons, but reduced subsequent long-term survival. Weakening of the SAC also reduced cell survival in response to spindle perturbation insufficient for triggering mitotic slippage, of which mitotic exit was characterized by displaced chromosomes during metaphase. In either mitotic slippage or mitotic exit with missegregated chromosomes, cell death occurred only after one cell cycle following mitotic exit and increased progressively during subsequent cell cycles. Consistent with these results, transient inhibition of the SAC using an MPS1 inhibitor acted synergistically with spindle perturbation in inducing chromosome missegregation and cytotoxicity. The specific temporal patterns of cell death after mitotic exit with weakened SAC may reconcile the contradictory results from many previous studies.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Zeng X,Xu WK,Lok TM,Ma HT,Poon RYC

doi

10.1038/s41419-019-1539-8

subject

Has Abstract

pub_date

2019-04-05 00:00:00

pages

314

issue

4

issn

2041-4889

pii

10.1038/s41419-019-1539-8

journal_volume

10

pub_type

杂志文章
  • WDR79 promotes the proliferation of non-small cell lung cancer cells via USP7-mediated regulation of the Mdm2-p53 pathway.

    abstract::WD repeat protein 79 (WDR79) is a member of the WD-repeat protein family and functions as a scaffold protein during telomerase assembly, Cajal body formation and DNA double strand break repair. We have previously shown that WDR79 is frequently overexpressed in cell lines and tissues derived from non-small cell lung ca...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.162

    authors: Sun Y,Cao L,Sheng X,Chen J,Zhou Y,Yang C,Deng T,Ma H,Feng P,Liu J,Tan W,Ye M

    更新日期:2017-04-13 00:00:00

  • RIP1 protects melanoma cells from apoptosis induced by BRAF/MEK inhibitors.

    abstract::Many recent studies have uncovered the necessary role for the receptor-interacting protein kinase 1 (RIP1) in regulating apoptosis and necrosis that cells undergo in response to various cellular stresses. However, the functional significance of RIP1 in promoting cancer cells survival remains poorly understood. Here, w...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0714-7

    authors: Lei FX,Jin L,Liu XY,Lai F,Yan XG,Farrelly M,Guo ST,Zhao XH,Zhang XD

    更新日期:2018-06-07 00:00:00

  • Correction: Aberrant iPSC-derived human astrocytes in Alzheimer's disease.

    abstract::The original version of this Article contained an error in Fig. 1, in which a number of incorrect fluorescence images were inadvertently incorporated into the panel. This has been corrected in both the PDF and HTML versions of the Article. ...

    journal_title:Cell death & disease

    pub_type: 已发布勘误

    doi:10.1038/s41419-019-1422-7

    authors: Jones VC,Atkinson-Dell R,Verkhratsky A,Mohamet L

    更新日期:2019-03-12 00:00:00

  • A long non-coding RNA interacts with Gfra1 and maintains survival of mouse spermatogonial stem cells.

    abstract::Spermatogonial stem cells (SSCs) are unique male germline stem cells that support spermatogenesis and male fertility. Long non-coding RNAs (lncRNA) have been identified as key regulators of stem cell fate; however, their role in SSCs has not been explored. Here, we report that a novel spermatogonia-specific lncRNA (ln...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.24

    authors: Li L,Wang M,Wang M,Wu X,Geng L,Xue Y,Wei X,Jia Y,Wu X

    更新日期:2016-03-10 00:00:00

  • Cryo-thermal therapy induces macrophage polarization for durable anti-tumor immunity.

    abstract::Many cancer therapies are being developed for the induction of durable anti-tumor immunity, especially for malignant tumors. The activation of antigen-presenting cells (APCs), including macrophages and dendritic cells (DCs), can bridge innate and adaptive immune responses against tumors. However, APCs have an immunosu...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1459-7

    authors: He K,Jia S,Lou Y,Liu P,Xu LX

    更新日期:2019-03-04 00:00:00

  • Renal cell carcinoma escapes death by p53 depletion through transglutaminase 2-chaperoned autophagy.

    abstract::In renal cell carcinoma, transglutaminase 2 (TGase 2) crosslinks p53 in autophagosomes, resulting in p53 depletion and the tumor's evasion of apoptosis. Inhibition of TGase 2 stabilizes p53 and induces tumor cells to enter apoptosis. This study explored the mechanism of TGase 2-dependent p53 degradation. We found that...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.14

    authors: Kang JH,Lee JS,Hong D,Lee SH,Kim N,Lee WK,Sung TW,Gong YD,Kim SY

    更新日期:2016-03-31 00:00:00

  • HMGB1 promotes ERK-mediated mitochondrial Drp1 phosphorylation for chemoresistance through RAGE in colorectal cancer.

    abstract::Dysfunctional mitochondria have been shown to enhance cancer cell proliferation, reduce apoptosis, and increase chemoresistance. Chemoresistance develops in nearly all patients with colorectal cancer, leading to a decrease in the therapeutic efficacies of anticancer agents. However, the effect of dynamin-related prote...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-1019-6

    authors: Huang CY,Chiang SF,Chen WT,Ke TW,Chen TW,You YS,Lin CY,Chao KSC,Huang CY

    更新日期:2018-09-26 00:00:00

  • MicroRNA-144 is regulated by CP2 and decreases COX-2 expression and PGE2 production in mouse ovarian granulosa cells.

    abstract::Mammalian folliculogenesis is a complex process in which primordial follicles develop into pre-ovulatory follicles, followed by ovulation to release mature oocytes. In this study, we explored the role of miR-144 in ovulation. miR-144 was one of the differentially expressed microRNAs, which showed 5.59-fold changes, in...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.24

    authors: Zhou J,Lei B,Li H,Zhu L,Wang L,Tao H,Mei S,Li F

    更新日期:2017-02-09 00:00:00

  • Manipulating the air-filled zebrafish swim bladder as a neutrophilic inflammation model for acute lung injury.

    abstract::Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS), are life-threatening diseases that are associated with high mortality rates due to treatment limitations. Neutrophils play key roles in the pathogenesis of ALI/ARDS by promoting the inflammation and injury of the alveolar mic...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.365

    authors: Zhang Y,Liu H,Yao J,Huang Y,Qin S,Sun Z,Xu Y,Wan S,Cheng H,Li C,Zhang X,Ke Y

    更新日期:2016-11-10 00:00:00

  • Inhibition of TXNIP expression in vivo blocks early pathologies of diabetic retinopathy.

    abstract::Evidence is mounting that proinflammatory and proapoptotic thioredoxin-interacting protein (TXNIP) has a causative role in the development of diabetes. However, there are no studies investigating the role of TXNIP in diabetic retinopathy (DR). Here, we show that, in diabetic rats, TXNIP expression and hexosamine biosy...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2010.42

    authors: Perrone L,Devi TS,Hosoya KI,Terasaki T,Singh LP

    更新日期:2010-08-19 00:00:00

  • Extracellular ATP drives systemic inflammation, tissue damage and mortality.

    abstract::Systemic inflammatory response syndromes (SIRS) may be caused by both infectious and sterile insults, such as trauma, ischemia-reperfusion or burns. They are characterized by early excessive inflammatory cytokine production and the endogenous release of several toxic and damaging molecules. These are necessary to figh...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.70

    authors: Cauwels A,Rogge E,Vandendriessche B,Shiva S,Brouckaert P

    更新日期:2014-03-06 00:00:00

  • Chloride channels are necessary for full platelet phosphatidylserine exposure and procoagulant activity.

    abstract::Platelets enhance thrombin generation at sites of vascular injury by exposing phosphatidylserine during necrosis-like cell death. Anoctamin 6 (Ano6) is required for Ca(2+)-dependent phosphatidylserine exposure and is defective in patients with Scott syndrome, a rare bleeding disorder. Ano6 may also form Cl(-) channels...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.495

    authors: Harper MT,Poole AW

    更新日期:2013-12-19 00:00:00

  • Melatonin inhibits apoptotic cell death induced by Vibrio vulnificus VvhA via melatonin receptor 2 coupling with NCF-1.

    abstract::Melatonin, an endogenous hormone molecule, has a variety of biological functions, but a functional role of melatonin in the infection of Gram-negative bacterium Vibrio vulnificus has yet to be described. In this study, we investigated the molecular mechanism of melatonin in the apoptosis of human intestinal epithelial...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-017-0083-7

    authors: Lee SJ,Lee HJ,Jung YH,Kim JS,Choi SH,Han HJ

    更新日期:2018-01-19 00:00:00

  • Wnt signaling induces radioresistance through upregulating HMGB1 in esophageal squamous cell carcinoma.

    abstract::Although many articles have uncovered that Wnt signaling is involved in radioresistance, the mechanism is rarely reported. Here we generated two radioresistant cells rECA109 and rKyse150 from parental esophageal cancer cells ECA109 and Kyse150. We then found that Wnt signaling activity was higher in radioresistant cel...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0466-4

    authors: Zhao Y,Yi J,Tao L,Huang G,Chu X,Song H,Chen L

    更新日期:2018-04-01 00:00:00

  • Upregulation of IGF2R evades lysosomal dysfunction-induced apoptosis of cervical cancer cells via transport of cathepsins.

    abstract::Cervical cancer is the most common gynecological malignancy in the world; however, the survival rates of advanced-stage and recurrent cervical cancer patients remain poor. The multifaced protein insulin-like growth factor 2 receptor (IGF2R) has various ligands, represented as IGF-2 and mannose-6-phosphate (M6P)-tagged...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-2117-9

    authors: Takeda T,Komatsu M,Chiwaki F,Komatsuzaki R,Nakamura K,Tsuji K,Kobayashi Y,Tominaga E,Ono M,Banno K,Aoki D,Sasaki H

    更新日期:2019-11-20 00:00:00

  • LINC00675 activates androgen receptor axis signaling pathway to promote castration-resistant prostate cancer progression.

    abstract::The development of prostate cancer (PCa) from androgen-deprivation therapy (ADT) sensitive to castration resistant (CRPC) seriously impacts life quality and survival of PCa patients. Emerging evidence shows that long noncoding RNAs (lncRNAs) play vital roles in cancer initiation and progression. However, the inherited...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-02856-5

    authors: Yao M,Shi X,Li Y,Xiao Y,Butler W,Huang Y,Du L,Wu T,Bian X,Shi G,Ye D,Fu G,Wang J,Ren S

    更新日期:2020-08-15 00:00:00

  • Circ_0002770, acting as a competitive endogenous RNA, promotes proliferation and invasion by targeting miR-331-3p in melanoma.

    abstract::Melanoma is a kind of tumor that originates from melanocytes and is characterized by chemoresistance and distant metastasis. Although the complete pathogenesis of melanoma remains unclear, increasing evidence suggests that circular RNAs (circRNAs) may be involved. In the present study, we identified a circular RNA, ci...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2444-x

    authors: Qian P,Linbo L,Xiaomei Z,Hui P

    更新日期:2020-04-23 00:00:00

  • A new inhibitor of glucose-6-phosphate dehydrogenase blocks pentose phosphate pathway and suppresses malignant proliferation and metastasis in vivo.

    abstract::Pentose phosphate pathway (PPP) is a major glucose metabolism pathway, which has a fundamental role in cancer growth and metastasis. Even though PPP blockade has been pointed out as a very promising strategy against cancer, effective anti-PPP agents are not still available in the clinical setting. Here we demonstrate ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0635-5

    authors: Mele L,Paino F,Papaccio F,Regad T,Boocock D,Stiuso P,Lombardi A,Liccardo D,Aquino G,Barbieri A,Arra C,Coveney C,La Noce M,Papaccio G,Caraglia M,Tirino V,Desiderio V

    更新日期:2018-05-01 00:00:00

  • Activation of the c-Jun NH2-terminal kinase pathway by coronavirus infectious bronchitis virus promotes apoptosis independently of c-Jun.

    abstract::Mitogen-activated protein kinases (MAPKs) are conserved protein kinases that regulate a variety of important cellular signaling pathways. Among them, c-Jun N-terminal kinases (JNK) are known to be activated by various environmental stresses including virus infections. Previously, activation of the JNK pathway has been...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-017-0053-0

    authors: Fung TS,Liu DX

    更新日期:2017-12-13 00:00:00

  • Direct impact of cisplatin on mitochondria induces ROS production that dictates cell fate of ovarian cancer cells.

    abstract::Patients with high-grade serous ovarian cancer (HGSC) frequently receive platinum-based chemotherapeutics, such as cisplatin. Cisplatin binds to DNA and induces DNA-damage culminating in mitochondria-mediated apoptosis. Interestingly, mitochondrial DNA is critically affected by cisplatin but its relevance in cell deat...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-2081-4

    authors: Kleih M,Böpple K,Dong M,Gaißler A,Heine S,Olayioye MA,Aulitzky WE,Essmann F

    更新日期:2019-11-07 00:00:00

  • Correction: Schwann cells support oncogenic potential of pancreatic cancer cells through TGFβ signaling.

    abstract::The original version of this article contained an error in the name of one of the co-authors (Kayvan Mohkam). This has been corrected in the PDF and HTML versions. ...

    journal_title:Cell death & disease

    pub_type: 已发布勘误

    doi:10.1038/s41419-020-2262-1

    authors: Roger E,Martel S,Bertrand-Chapel A,Depollier A,Chuvin N,Pommier RM,Yacoub K,Caligaris C,Cardot-Ruffino V,Chauvet V,Aires S,Mohkam K,Mabrut JY,Adham M,Fenouil T,Hervieu V,Broutier L,Castets M,Neuzillet C,Cassier PA,

    更新日期:2020-01-23 00:00:00

  • PKCθ-JunB axis via upregulation of VEGFR3 expression mediates hypoxia-induced pathological retinal neovascularization.

    abstract::Pathological retinal neovascularization is the most common cause of vision loss. PKCθ has been shown to play a role in type 2 diabetes, which is linked to retinal neovascularization. Based on these clues, we have studied the role of PKCθ and its downstream target genes JunB and VEGFR3 in retinal neovascularization usi...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2522-0

    authors: Kumar R,Mani AM,Singh NK,Rao GN

    更新日期:2020-05-07 00:00:00

  • The transient expression of miR-203 and its inhibiting effects on skeletal muscle cell proliferation and differentiation.

    abstract::Previous studies have shown that miR-203 is a skin-specific microRNA (miRNA) with a profound role in skin cell differentiation. However, emerging microarray and deep sequencing data revealed that miR-203 is also expressed in embryonic skeletal muscle and myoblasts. In this study, we found that miR-203 was transiently ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.289

    authors: Luo W,Wu H,Ye Y,Li Z,Hao S,Kong L,Zheng X,Lin S,Nie Q,Zhang X

    更新日期:2014-07-17 00:00:00

  • Cell death-based treatments of melanoma:conventional treatments and new therapeutic strategies.

    abstract::The incidence of malignant melanoma has continued to rise during the past decades. However, in the last few years, treatment protocols have significantly been improved thanks to a better understanding of the key oncogenes and signaling pathways involved in its pathogenesis and progression. Anticancer therapy would eit...

    journal_title:Cell death & disease

    pub_type: 杂志文章,评审

    doi:10.1038/s41419-017-0059-7

    authors: Mattia G,Puglisi R,Ascione B,Malorni W,Carè A,Matarrese P

    更新日期:2018-01-25 00:00:00

  • The SGK3-triggered ubiquitin-proteasome degradation of podocalyxin (PC) and ezrin in podocytes was associated with the stability of the PC/ezrin complex.

    abstract::Podocyte damage is commonly accompanied by destabilization of the podocalyxin (PC)/ezrin complex. Serum- and glucocorticoid-inducible kinase 3 (SGK3) plays a role in the maintenance of podocyte function, but the details of this role are poorly understood. Herein we demonstrated that SGK3 and its downstream target prot...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-1161-1

    authors: Yuan YP,Zhao H,Peng LQ,Li ZF,Liu S,Yuan CY,Mwamunyi MJ,Pearce D,Yao LJ

    更新日期:2018-11-01 00:00:00

  • DJ-1 modulates the unfolded protein response and cell death via upregulation of ATF4 following ER stress.

    abstract::The unfolded protein response (UPR) triggered by endoplasmic reticulum (ER) stress is a feature of many neurodegenerative diseases including Alzheimer's disease, Huntington's disease and Parkinson's disease (PD). Although the vast majority of PD is sporadic, mutations in a number of genes including PARK7 which encodes...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1354-2

    authors: Yang J,Kim KS,Iyirhiaro GO,Marcogliese PC,Callaghan SM,Qu D,Kim WJ,Slack RS,Park DS

    更新日期:2019-02-12 00:00:00

  • SIRT1 activation enhances HDAC inhibition-mediated upregulation of GADD45G by repressing the binding of NF-κB/STAT3 complex to its promoter in malignant lymphoid cells.

    abstract::We explored the activity of SIRT1 activators (SRT501 and SRT2183) alone and in combination with panobinostat in a panel of malignant lymphoid cell lines in terms of biological and gene expression responses. SRT501 and SRT2183 induced growth arrest and apoptosis, concomitant with deacetylation of STAT3 and NF-κB, and r...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.159

    authors: Scuto A,Kirschbaum M,Buettner R,Kujawski M,Cermak JM,Atadja P,Jove R

    更新日期:2013-05-16 00:00:00

  • miR-302 regulates pluripotency, teratoma formation and differentiation in stem cells via an AKT1/OCT4-dependent manner.

    abstract::Pluripotency makes human pluripotent stem cells (hPSCs) promising for regenerative medicine, but the teratoma formation has been considered to be a major obstacle for their clinical applications. Here, we determined that the downregulation of miR-302 suppresses the teratoma formation, hampers the self-renewal and plur...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2015.383

    authors: Li HL,Wei JF,Fan LY,Wang SH,Zhu L,Li TP,Lin G,Sun Y,Sun ZJ,Ding J,Liang XL,Li J,Han Q,Zhao RC

    更新日期:2016-01-28 00:00:00

  • Circulating microRNAs in breast cancer: novel diagnostic and prognostic biomarkers.

    abstract::Effective management of breast cancer depends on early diagnosis and proper monitoring of patients' response to therapy. However, these goals are difficult to achieve because of the lack of sensitive and specific biomarkers for early detection and for disease monitoring. Accumulating evidence in the past several years...

    journal_title:Cell death & disease

    pub_type: 杂志文章,评审

    doi:10.1038/cddis.2017.440

    authors: Hamam R,Hamam D,Alsaleh KA,Kassem M,Zaher W,Alfayez M,Aldahmash A,Alajez NM

    更新日期:2017-09-07 00:00:00

  • Argonaute 2 sustains the gene expression program driving human monocytic differentiation of acute myeloid leukemia cells.

    abstract::MicroRNAs are key regulators of many biological processes, including cell differentiation. These small RNAs exert their function assembled in the RNA-induced silencing complexes (RISCs), where members of Argonaute (Ago) family of proteins provide a unique platform for target recognition and gene silencing. Here, by us...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.452

    authors: Iosue I,Quaranta R,Masciarelli S,Fontemaggi G,Batassa EM,Bertolami C,Ottone T,Divona M,Salvatori B,Padula F,Fatica A,Lo-Coco F,Nervi C,Fazi F

    更新日期:2013-11-21 00:00:00