BUB1 plays a key role in promoting TGF-β signaling


The aberrant of transforming growth factor-β (TGF-β) signaling is related to many disorders, including inflammatory disease, tumor formation and metastasis. By using human kinome siRNA screen and a live-cell reporter for TGF-β receptor (TGFBR) activity, Nyati et al. identified the kinase budding uninhibited by benzimidazoles-1 (BUB1) plays a critical role in regulating TGF-β signaling. The article was published on Science Signaling.


BUB1 is a serine/theronine kinase that mediating mitotic spindle checkpoint establishment and chromosome alignment. In this study, researchers found BUB1 knockdown induced the most robust downregulation of TGF-β-dependent transcription factors such as SMAD2, SMAD3, and other noncanonical signaling cascade, indicating that BUB1 promotes TGF-β signaling pathway. In addition, BUB1 interacts with TGFBRI and promotes TGF-β-dependent TGFBRI-TGFBRII heteromeric complex formation. Also, BUB1 interacts with TGFBRII to help the formation of ternary complex. In various cell lines, 2OH-BNPP1, a BUB1 kinase activity specific inhibitor, and a kinase-deficient mutant of BUB1 suppressed TGF-β signaling and ternary complex formation, indicating the effects of BUB1 on TGF-β signaling pathway depend on the kinase activity of BUB1. The findings broaden the previous view of BUB1 on regulating cell cycle and chromosome cohesion, suggesting BUB1 also plays a key role in promoting TGF-β.


Sci Signal. 2015 Jan 6;8(358):ra1.