Research ArticleCancer

The kinase activity of the Ser/Thr kinase BUB1 promotes TGF-β signaling

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Science Signaling  06 Jan 2015:
Vol. 8, Issue 358, pp. ra1
DOI: 10.1126/scisignal.2005379

Placing BUB1 in the TGF-β Pathway

The transforming growth factor–β (TGF-β) pathway regulates cell proliferation and migration, processes involved in development, regeneration, and tumorigenesis. The kinase BUB1, which promotes proper chromosome alignment as cells prepare to divide, also regulates cell proliferation. Nyati et al. connected BUB1 to TGF-β signaling. They found that knocking down BUB1 impaired TGF-β–mediated proliferation of tumor cells—but not by acting at chromosomes. Instead, cytoplasmic BUB1 interacted with TGF-β receptor subunits at the cell surface, promoting the interaction between receptor subunits and between the receptor and downstream signaling proteins. Inhibiting the kinase activity of BUB1 suppressed TGF-β pathway activity in cells in culture and in xenografts. The findings suggest a possible point of crosstalk between the mitotic checkpoint and TGF-β signaling.