Journal article
UBASH3B-mediated silencing of the mitotic checkpoint: Therapeutic perspectives in cancer
Molecular & cellular oncology, Vol.5(2), p.e1271494
03/04/2018
DOI: 10.1080/23723556.2016.1271494
PMID: 29487893
Abstract
Defects in mitosis can lead to aneuploidy, which is a common feature of human cancers. Spindle Assembly Checkpoint (SAC) controls fidelity of chromosome segregation in mitosis to prevent aneuploidy. The ubiquitin receptor protein Ubiquitin Associated and SH3 Domain Containing B (UBASH3B) was recently found to control SAC silencing and faithful chromosome segregation by relocalizing Aurora B kinase to the mitotic microtubules. Accordingly, loss and gain of function of UBASH3B have strong effects on mitotic progression. Downregulation of UBASH3B prevents SAC satisfaction leading to inhibition of chromosome segregation, mitotic arrest, and cell death. In contrast, increased cellular levels of UBASH3B trigger premature and uncontrolled chromosome segregation. Interestingly, elevated levels of UBASH3B were found in aggressive tumors. Therefore, we raised the question whether the oncogenic potential of UBASH3B is linked to its role in chromosome segregation. Here we show that in cancer cells expressing high levels of UBASH3B and SAC proteins, downregulation of UBASH3B, can further potentiate SAC response inducing mitotic arrest and cell death. Moreover, data mining approaches identified a correlation between mRNA levels of UBASH3B and SAC components in a set of primary patient tumors including kidney and liver carcinomas. Thus, inhibition of UBASH3B may offer an attractive therapeutic perspective for cancers.
Details
- Title: Subtitle
- UBASH3B-mediated silencing of the mitotic checkpoint: Therapeutic perspectives in cancer
- Creators
- Ksenia Krupina - Université de StrasbourgCharlotte Kleiss - Institut de génétique et de biologie moléculaire et cellulaireSushil Awal - Institut de génétique et de biologie moléculaire et cellulaireIrene Rodriguez-Hernandez - King's College LondonVictoria Sanz-Moreno - King's College LondonIzabela Sumara - Institut de génétique et de biologie moléculaire et cellulaire
- Resource Type
- Journal article
- Publication Details
- Molecular & cellular oncology, Vol.5(2), p.e1271494
- DOI
- 10.1080/23723556.2016.1271494
- PMID
- 29487893
- NLM abbreviation
- Mol Cell Oncol
- ISSN
- 2372-3556
- eISSN
- 2372-3548
- Publisher
- Taylor & Francis
- Number of pages
- 8
- Grant note
- IGBMC ANR-10-LABX-0030-INRT; ANR-10-IDEX-0002-02 / French State fund Conectus Alsace; Region Grand-Est Fundacion Alfonso Martin Escudero RG110591 / Royal Society; Royal Society UK CNRS; Centre National de la Recherche Scientifique (CNRS) 24478; 12065 / Cancer Research UK La Ligue Contre le Cancer and University of Strasbourg Institute of Advanced Studies; Universite de Strasbourg Fondation ARC pour la recherche sur le cancer, Institut National du Cancer (INCa) MGU0418 / Barts Charity
- Language
- English
- Date published
- 03/04/2018
- Academic Unit
- Biochemistry and Molecular Biology
- Record Identifier
- 9985134036502771
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