IndraLab

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OTUD6B increases the amount of KIFC1. 6 / 6
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"As initial validation, transfection with these siRNA pools was repeated once more, confirming that depletion of USP3, OTUD6B, JOSD2, or UCHL1 decreased KIFC1 protein levels (Fig. 1E)."
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"OTUD6B modulates KIFC1 level and centrosome clustering in panel of breast cell lines."
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"The immortalised breast epithelial cell line hTERT-HME1 was used as a normal tissue comparator that has low centrosome amplification (Fig. EV1A) but, as in TNBC, OTUD6B depletion leads to reduced KIFC1 levels (Fig. EV2G)."
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"Together, these findings highlight OTUD6B as a DUB that maintains KIFC1 levels to ensure supernumerary centrosomes remain clustered, allowing cancer cells to avoid mitotic catastrophe and complete cell division.Amongst the 94 DUBs screened, we found that depletion of only OTUD6B or JOSD2 could both reduce cellular KIFC1 levels and increase multipolar spindles in TNBC cells (Figs."
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"This may also account for the observation that WT OTUD6B re-expression can rescue KIFC1 levels in interphase cells depleted of OTUD6B (Fig. 3D,E)."
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"Importantly, OTUD6B depletion could reduce KIFC1 expression in other cancer cell lines: MDA-MB-231, another TNBC cell line with moderate centrosome amplification, U2OS osteosarcoma cells that were originally used to demonstrate KIFC1 ubiquitination by the APC/C (Min et al, 2014), as well as in hTERT-HME1 as a model of immortalised normal breast epithelium (Fig. EV2E–G)."
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