UBASH3B-mediated silencing of the mitotic checkpoint: Therapeutic perspectives in cancer

Molecular & Cellular Oncology
Ksenia KrupinaIzabela Sumara

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 an...Continue Reading

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Citations

Aug 2, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Katerina JerabkovaIzabela Sumara

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Methods Mentioned

BETA
MDA
surgical resection

Software Mentioned

GraphPad Prism
cBioportal

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