Editors' ChoiceCell Biology

New connections: Moonlighting proteins, YAP and BUB1

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Sci. Signal.  01 Mar 2016:
Vol. 9, Issue 417, pp. ec48
DOI: 10.1126/scisignal.aaf5510

An emerging theme in regulatory biology is the identification of “noncanonical” mechanisms of activation of downstream effectors and “noncanonical” roles of signaling proteins. This week’s issue of Science Signaling includes a paper that describes one of these “moonlighting” functions for the protein YAP, which is best known as a transcriptional regulator involved in the regulation of cell size and proliferation downstream of the Hippo kinase cascade. Bui et al. discovered a role for YAP in mitotic cells. The cell cycle kinase CDK1 phosphorylated YAP, which directed YAP to the site of cytokinesis. Cells that could not direct YAP to the cytokinesis midbody failed to recruit proteins associated with regulation of the contraction needed to divide the cells into the two separate daughters. Thus, in interphase YAP functions as a transcriptional regulator, whereas in mitotic cells YAP helps organize the cytokinesis machinery. In a similar study, Nyati et al. found an unexpected association of the cell cycle kinase BUB1 with the receptor complex for transforming growth factor–β (TGF-β). In mitotic cells, BUB1 promotes chromosome alignment at the spindle and is necessary to ensure that each daughter cell gets the correct complement of chromosomes. BUB1 now has a role in interphase cells, where it interacts with TGF-β receptors, stabilizes the ligand-bound receptor complex, and promotes downstream signaling. Maybe we should be less surprised that proteins have different regulatory functions in dividing cells and nondividing cells; because the subcellular organization is so different in these contexts, proteins will have opportunities to interact with different partners. Science Signaling is interested in studies that investigate these moonlighting functions and anticipates that the terms “canonical” and “noncanonical” will have less and less meaning as more researchers explore different readouts of regulatory proteins and networks.

D. A. Bui, W. Lee, A. E. White, J. W. Harper, R. C. J. Schackmann, M. Overholtzer, L. M. Selfors, J. S. Brugge, Cytokinesis involves a nontranscriptional function of the Hippo pathway effector YAP. Sci. Signal. 9, ra23 (2016). [Full Text]

S. Nyati, K. Schinske-Sebolt, S. Pitchiaya, K. Chekhovskiy, A. Chator, N. Chaudhry, J. Dosch, M. E. Van Dort, S. Varambally, C. Kumar-Sinha, M. K. Nyati, D. Ray, N. G. Walter, H. Yu, B. D. Ross, A. Rehemtulla, The kinase activity of the Ser/Thr kinase BUB1 promotes TGF-β signaling. Sci. Signal. 8, ra1 (2015). [Full Text]