Aurora B phosphorylates Bub1 to promote spindle assembly checkpoint signaling

Roy, Babhrubahan; Han, Simon J. Y.; Fontan, Adrienne N.; Jema, Soubhagyalaxmi; Joglekar, Ajit P.

doi:10.1016/j.cub.2021.10.049

Cited by 28 publications

(28 citation statements)

References 71 publications

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“…However, BubR1 is unlikely to be recruited to budding yeast kinetochores ( Tromer et al. , 2016 ; Roy et al. , 2022 ), and in nocodazole-treated HeLa cells, the disruption of Bub1-mediated BubR1 recruitment slightly strengthens the SAC ( Overlack et al.…”

Section: Resultsmentioning

confidence: 99%

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BubR1 recruitment to the kinetochore via Bub1 enhances spindle assembly checkpoint signaling

Banerjee

Chen

Humphrey

et al. 2022

MBoC

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Section: Resultsmentioning

confidence: 99%

“…Importantly, the extended mitosis was due to increased Mad2-Cdc20 and MCC formation in HeLa cells and fission yeast ( Leontiou et al. , 2019 ; Roy et al. , 2022 ).…”

Section: Resultsmentioning

confidence: 99%

BubR1 recruitment to the kinetochore via Bub1 enhances spindle assembly checkpoint signaling

Banerjee

Chen

Humphrey

et al. 2022

MBoC

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“…Whether Aurora B activates mitotic checkpoint signaling solely by releasing inappropriate attachments to produce unattached kinetochores during error correction or participates directly in checkpoint signaling has been debated in the field. However, on balance, recent evidence favors the conclusion that Aurora B functions in mitotic checkpoint signaling independent of error correction in multiple species ( Kallio et al, 2002 ; Petersen and Hagan, 2003 ; Vader et al, 2007 ; Santaguida et al, 2011 ; Hadders et al, 2020 ; Roy et al, 2022 ). Our evidence supports this conclusion, and demonstrates that increased Aurora B, which reduces Aurora B substrate phosphorylation, also weakens mitotic checkpoint signaling in response to unattached kinetochores.…”

Section: Discussionmentioning

confidence: 98%

“…Early work reported that Aurora B was necessary to activate the mitotic checkpoint in response to lack of tension caused by taxol, but not in response to unattached kinetochores caused by loss of microtubules ( Biggins et al, 1999 ; Biggins and Murray, 2001 ; Carvalho et al, 2003 ; Pinsky et al, 2006 ). However, others have reported that Aurora B also functions directly in mitotic checkpoint activation, even in the absence of microtubules, and contributes to formation of mitotic checkpoint complexes ( Santaguida et al, 2011 ; Matson et al, 2012 ; Matson and Stukenberg, 2014 ; Hadders et al, 2020 ; Roy et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Increased Aurora B expression reduces substrate phosphorylation and induces chromosomal instability

Britigan

Wan

Sam

et al. 2022

Front. Cell Dev. Biol.

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Increased Aurora B protein expression, which is common in cancers, is expected to increase Aurora B kinase activity, yielding elevated phosphorylation of Aurora B substrates. In contrast, here we show that elevated expression of Aurora B reduces phosphorylation of six different Aurora B substrates across three species and causes defects consistent with Aurora B inhibition. Complexes of Aurora B and its binding partner INCENP autophosphorylate in trans to achieve full Aurora B activation. Increased expression of Aurora B mislocalizes INCENP, reducing the local concentration of Aurora B:INCENP complexes at the inner centromere/kinetochore. Co-expression of INCENP rescues Aurora B kinase activity and mitotic defects caused by elevated Aurora B. However, INCENP expression is not elevated in concert with Aurora B in breast cancer, and increased expression of Aurora B causes resistance rather than hypersensitivity to Aurora B inhibitors. Thus, increased Aurora B expression reduces, rather than increases, Aurora B kinase activity.

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“…Recent studies have shown that CDC20 promotes several types of cancer progression, including glioma and lung cancer ( Wang et al, 2013 ; Wang et al, 2015 ). Aurora B phosphorylates BUB1 to facilitate spindle assembly checkpoint signaling, and target Aurora B kinase can prevent and overcome resistance to EGFR inhibitors in lung cancer ( Tanaka et al, 2021 ; Roy et al, 2022 ). KIF11, known as mitotic spindle-specific protein, and its oral inhibitor 4SC-205 demonstrates anti-tumor activity and enhances targeted therapy in primary and metastatic neuroblastoma models ( Masanas et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Identification and verification of hub genes associated with the progression of non-small cell lung cancer by integrated analysis

et al. 2022

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Objectives: Lung cancer is one of the most common cancers worldwide and it is the leading cause of cancer-related mortality. Despite the treatment of patients with non-small cell lung carcinoma (NSCLC) have improved, the molecular mechanisms of NSCLC are still to be further explored.Materials and Methods: Microarray datasets from the Gene Expression Omnibus (GEO) database were selected to identify the candidate genes associated with tumorigenesis and progression of non-small cell lung carcinoma. The differentially expressed genes (DEGs) were identified by GEO2R. Protein-protein interaction network (PPI) were used to screen out hub genes. The expression levels of hub genes were verified by GEPIA, Oncomine and The Human Protein Atlas (HPA) databases. Survival analysis and receiver operating characteristic (ROC) curve analysis were performed to value the importance of hub genes in NSCLC diagnosis and prognosis. ENCODE and cBioPortal were used to explore the upstream regulatory mechanisms of hub genes. Analysis on CancerSEA Tool, CCK8 assay and colony formation assay revealed the functions of hub genes in NSCLC.Results: A total of 426 DEGs were identified, including 93 up-regulated genes and 333 down-regulated genes. And nine hub genes (CDC6, KIAA0101, CDC20, BUB1B, CCNA2, NCAPG, KIF11, BUB1 and CDK1) were found to increase with the tumorigenesis, progression and cisplatin resistance of NSCLC, especially EGFR- or KRAS-mutation driven NSCLC. Hub genes were valuable biomarkers for NSCLC, and the overexpression of hub genes led to poor survival of NSCLC patients. Function analysis showed that hub genes played roles in cell cycle and proliferation, and knockdown of hub genes significantly inhibited A549 and SPCA1 cell growth. Further exploration demonstrated that copy number alterations (CNAs) and transcription activation may account for the up-regulation of hub genes.Conclusion: Hub genes identified in this study provided better understanding of molecular mechanisms within tumorigenesis and progression of NSCLC, and provided potential targets for NSCLC treatment as well.

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Aurora B phosphorylates Bub1 to promote spindle assembly checkpoint signaling

Abstract: Aurora B phosphorylates Bub1 to promote spindle assembly checkpoint signaling Highlights d Aurora B cannot activate the SAC because it cannot phosphorylate Knl1 ''MELT'' motifs d Aurora B promotes SAC signaling by phosphorylating Bub1 d Aurora B activity promotes Mad1 recruitment via Bub1

Cited by 28 publications

References 71 publications

BubR1 recruitment to the kinetochore via Bub1 enhances spindle assembly checkpoint signaling

BubR1 recruitment to the kinetochore via Bub1 enhances spindle assembly checkpoint signaling

Increased Aurora B expression reduces substrate phosphorylation and induces chromosomal instability

Identification and verification of hub genes associated with the progression of non-small cell lung cancer by integrated analysis

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