Deregulation of the spindle assembly checkpoint is associated with paclitaxel resistance in ovarian cancer

Chong, Taryne; Sarac, Amila; Yao, Cindy Q.; Liao, Linda M.; Lyttle, Nicola; Boutros, Paul C.; Bartlett, John M.S.; Spears, Melanie

doi:10.1186/s13048-018-0399-7

Cited by 29 publications

(22 citation statements)

References 29 publications

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“…The prolonged metaphase-anaphase transition we observe in RepIDdepleted cells correlates with the increased sensitivity to PTX of cells depleted in RepID/CRL4 RBBP7 or overexpressing BUB3. This finding is in line with the observed PTX resistance of BUB1depleted ovarian cancer cells 59 and in mice depleted of MAD2 and BUBR1 60 . The increased population of cells in subG1 phase observed after BUB3-overespressing cells were released from nocodazole also implies that prolonged delays in mitotic exit might lead to cell death.…”

Section: Discussionsupporting

confidence: 89%

The RepID–CRL4 ubiquitin ligase complex regulates metaphase to anaphase transition via BUB3 degradation

Jang

Nathans

et al. 2020

Nat Commun

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The spindle assembly checkpoint (SAC) prevents premature chromosome segregation by inactivating the anaphase promoting complex/cyclosome (APC/C) until all chromosomes are properly attached to mitotic spindles. Here we identify a role for Cullin-RING ubiquitin ligase complex 4 (CRL4), known for modulating DNA replication, as a crucial mitotic regulator that triggers the termination of the SAC and enables chromosome segregation. CRL4 is recruited to chromatin by the replication origin binding protein RepID/DCAF14/PHIP. During mitosis, CRL4 dissociates from RepID and replaces it with RB Binding Protein 7 (RBBP7), which ubiquitinates the SAC mediator BUB3 to enable mitotic exit. During interphase, BUB3 is protected from CRL4-mediated degradation by associating with promyelocytic leukemia (PML) nuclear bodies, ensuring its availability upon mitotic onset. Deficiencies in RepID, CRL4 or RBBP7 delay mitotic exit, increase genomic instability and enhance sensitivity to paclitaxel, a microtubule stabilizer and anti-tumor drug.

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Section: Discussionsupporting

confidence: 89%

The RepID–CRL4 ubiquitin ligase complex regulates metaphase to anaphase transition via BUB3 degradation

Jang

Nathans

et al. 2020

Nat Commun

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“…Inhibition of mitotic slippage by inactivation of APC/C by RNAi, Apcin, or pro-TAME may increase the sensitivity of tumor cells to anti-microtubule agents ( Huang et al, 2009 ; Raab et al, 2019 ; Sackton et al, 2014 ). In this study, we found that cells upon SAG knockdown had reduced levels of mitotic-regulation proteins, such as cyclinB1 and Aurora A, an observation similar to cells with developed paclitaxel resistance ( Chong et al, 2018 ). Consequently, these SAG knockdown cells become resistance to apoptosis induced by nocodazole/taxol.…”

Section: Discussionsupporting

confidence: 52%

The Negative Cross-Talk between SAG/RBX2/ROC2 and APC/C E3 Ligases in Regulation of Cell Cycle Progression and Drug Resistance

Zhang

Shen

et al. 2020

Cell Reports

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SUMMARY Anaphase-promoting complex/cyclosome (APC/C) is a well-characterized E3 ligase that couples with UBE2C and UBE2S E2s for substrate ubiquitylation by the K11 linkage. Our recent data show that SAG/RBX2/ROC2, a RING component of Cullin-RING E3 ligase, also complexes with these E2s for K11-linked substrate polyubiquitylation. Whether these two E3s cross-talk with each other was previously unknown. Here, we report that SAG competes with APC2 for UBE2C/UBE2S binding to act as a potential endogenous inhibitor of APC/C, thereby regulating the G2-to-M progression. As such, SAG knockdown triggers premature activation of APC/C, leading to mitotic slippage and resistance to anti-microtubule drugs. On the other hand, SAG itself is a substrate of APC/C CDH1 for targeted degradation at the G1 phase. The degradation-resistant mutant of SAG-R98A/L101A accelerates the G1-to-S progression. Our study reveals that the negative cross-talk between SAG and APC/C is likely a mechanism to ensure the fidelity of cell cycle progression.

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“…In invasive ductal carcinoma, CENPE was identified to be one of the top ten potential crucial genes (29). In addition, studies have identified that the expression of CENPE is associated with drug tolerance (30)(31)(32). In paclitaxel-resistant ovarian cell lines, it was revealed that CENPE expression is lower (31).…”

Section: Discussionmentioning

confidence: 99%

CENPE promotes lung adenocarcinoma proliferation and is directly regulated by FOXM1

Shan

Zhao

et al. 2019

Int J Oncol

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Lung cancer is the most common and most lethal type of cancer. A sustained proliferative capacity is one of the hallmarks of cancer, and microtubules serve an important role in maintaining a sustained cell cycle. Therefore, understanding the regulation of microtubule proteins in the cell cycle is important for tumor prevention and treatment. Centromere protein E (CENPE) is a human kinetochore protein that is highly expressed in the G2/M phase of the cell cycle. The present study identified that CENPE is highly expressed in lung adenocarcinoma (LUAD) tissues. Following knockdown of CENPE expression, the proliferation of lung cancer cells was inhibited. In addition, it was revealed that forkhead box M1 (FOXM1) is significantly correlated with CENE expression. Following FOXM1-knockdown, the expression level of CENPE was decreased and the proliferation of lung cancer cells was inhibited. Overexpression of FOXM1 promoted the expression of CENPE and the proliferation of lung cancer cells. A chromatin immunoprecipitation assay identified that FOXM1 binds directly to the promoter region of CENPE. Therefore, the present data demonstrated that CENPE can promote the proliferation of LUAD cells and is directly regulated by FOXM1.

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Deregulation of the spindle assembly checkpoint is associated with paclitaxel resistance in ovarian cancer

Cited by 29 publications

References 29 publications

The RepID–CRL4 ubiquitin ligase complex regulates metaphase to anaphase transition via BUB3 degradation

The RepID–CRL4 ubiquitin ligase complex regulates metaphase to anaphase transition via BUB3 degradation

The Negative Cross-Talk between SAG/RBX2/ROC2 and APC/C E3 Ligases in Regulation of Cell Cycle Progression and Drug Resistance

CENPE promotes lung adenocarcinoma proliferation and is directly regulated by FOXM1

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