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- Co-silencing of human Bub3 and dynein highlights an antagonistic relationship in regulating kinetochore-microtubule attachmentsPublication . Silva, Patricia M. A.; Tavares, Alvaro A.; Bousbaa, HassanWe previously reported that the spindle assembly checkpoint protein Bub3 is involved in regulating kinetochore-microtubule (KT-MT) attachments. Also, Bub3 was reported to interact with the microtubule motor protein dynein. Here we examined how this interaction contributes to KT-MT attachments. Depletion of Bub3 or dynein induced misaligned chromosomes, consistent with their role in KT-MT attachments. Unexpectedly, co-silencing of both proteins partially suppressed the misalignment phenotype and restored chromosome congression. Consistent with these observations, KT-MT attachments in co-depleted cells were stable, able to drive chromosome congression, and produce inter-and intra-kinetochore stretch, indicating they are functional. We suggest that a mutual antagonism exists between Bub3 and dynein to ensure optimal KT-MT attachments. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
- Spindly and Bub3 expression in oral cancer: Prognostic and therapeutic implicationsPublication . Silva, Patricia M. A.; Delgado, Maria Leonor; Ribeiro, Nilza; Florindo, Claudia; Tavares, Alvaro A.; Ribeiro, Diana; Lopes, Carlos; do Amaral, Barbas; Bousbaa, Hassan; Monteiro, Luis SilvaObjectives Bub3 and Spindly are essential proteins required for the activation and inactivation of the spindle assembly checkpoint, respectively. Here, we explored the clinicopathological significance and the therapeutic potential of the opposing roles of the two proteins in oral squamous cell carcinoma (OSCC). Materials and Methods Bub3 and Spindly expression was evaluated by immunohistochemistry in 62 tissue microarrays from OSCC and by real-time PCR in OSCC cell lines and in normal human oral keratinocytes. The results were analyzed as to their clinicopathological significance. RNA interference-mediated Spindly or Bub3 inhibition was combined with cisplatin treatment, and the effect on the viability of OSCC cells was assessed. Results Overexpression of Bub3 and Spindly was detected in OSCC patients. High expression of Spindly, Bub3, or both was an independent prognostic indicator for cancer-specific survival and was associated with increased cellular proliferation. Accordingly, Bub3 and Spindly were upregulated in OSCC cells comparatively to their normal counterpart. Inhibition of Bub3 or Spindly was cytotoxic to OSCC cells and enhanced their chemosensitivity to cisplatin. Conclusions The data point out Bub3 and Spindly as potential markers of proliferation and prognosis, and highlight the potential therapeutic benefit of combining their inhibition with cisplatin.