Tags

Type your tag names separated by a space and hit enter

Cytokinesis involves a nontranscriptional function of the Hippo pathway effector YAP.
Sci Signal. 2016 Mar 01; 9(417):ra23.SS

Abstract

YAP is a transcriptional coactivator that controls organ expansion and differentiation and is inhibited by the Hippo pathway in cells in interphase. Here, we demonstrated that, during mitosis, YAP localized to the midbody and spindle, subcellular structures that are involved in cytokinesis, the process by which contraction of the cytoskeleton produces two daughter cells. Furthermore, YAP was phosphorylated by CDK1, a kinase that promotes cell cycle progression. Knockdown of YAP by shRNA or expression of a nonphosphorylatable form of YAP delayed the separation of daughter cells (called abscission) and induced a cytokinesis phenotype associated with increased contractile force, membrane blebbing and bulges, and abnormal spindle orientation. Consequently, these defects led to an increased frequency of multinucleation, micronuclei, and aneuploidy. YAP was required for proper localization of proteins that regulate contraction during cytokinesis, including ECT2, MgcRacGap, Anillin, and RHOA. In addition, depletion of YAP increased the phosphorylation of myosin light chain, which would be expected to activate the contractile activity of myosin II, the molecular motor involved in cytokinesis. The polarity scaffold protein PATJ coprecipitated with YAP and colocalized with YAP at the cytokinesis midbody, and knockdown of PATJ phenocopied the cytokinetic defects and spindle orientation alterations induced by either YAP depletion or expression of a nonphosphorylatable YAP mutant. Together, these results reveal an unanticipated role for YAP in the proper organization of the cytokinesis machinery during mitosis through interaction with the polarity protein PATJ.

Authors+Show Affiliations

Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.The Ronald O. Perelman Department of Dermatology and the Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA.Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.BCMB (Biochemistry, Cell, and Molecular Biology) Allied Program, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA. Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. joan_brugge@hms.harvard.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26933062

Citation

Bui, Duyen Amy, et al. "Cytokinesis Involves a Nontranscriptional Function of the Hippo Pathway Effector YAP." Science Signaling, vol. 9, no. 417, 2016, pp. ra23.
Bui DA, Lee W, White AE, et al. Cytokinesis involves a nontranscriptional function of the Hippo pathway effector YAP. Sci Signal. 2016;9(417):ra23.
Bui, D. A., Lee, W., White, A. E., Harper, J. W., Schackmann, R. C., Overholtzer, M., Selfors, L. M., & Brugge, J. S. (2016). Cytokinesis involves a nontranscriptional function of the Hippo pathway effector YAP. Science Signaling, 9(417), ra23. https://doi.org/10.1126/scisignal.aaa9227
Bui DA, et al. Cytokinesis Involves a Nontranscriptional Function of the Hippo Pathway Effector YAP. Sci Signal. 2016 Mar 1;9(417):ra23. PubMed PMID: 26933062.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cytokinesis involves a nontranscriptional function of the Hippo pathway effector YAP. AU - Bui,Duyen Amy, AU - Lee,Wendy, AU - White,Anne E, AU - Harper,J Wade, AU - Schackmann,Ron C J, AU - Overholtzer,Michael, AU - Selfors,Laura M, AU - Brugge,Joan S, Y1 - 2016/03/01/ PY - 2016/3/3/entrez PY - 2016/3/5/pubmed PY - 2016/12/15/medline SP - ra23 EP - ra23 JF - Science signaling JO - Sci Signal VL - 9 IS - 417 N2 - YAP is a transcriptional coactivator that controls organ expansion and differentiation and is inhibited by the Hippo pathway in cells in interphase. Here, we demonstrated that, during mitosis, YAP localized to the midbody and spindle, subcellular structures that are involved in cytokinesis, the process by which contraction of the cytoskeleton produces two daughter cells. Furthermore, YAP was phosphorylated by CDK1, a kinase that promotes cell cycle progression. Knockdown of YAP by shRNA or expression of a nonphosphorylatable form of YAP delayed the separation of daughter cells (called abscission) and induced a cytokinesis phenotype associated with increased contractile force, membrane blebbing and bulges, and abnormal spindle orientation. Consequently, these defects led to an increased frequency of multinucleation, micronuclei, and aneuploidy. YAP was required for proper localization of proteins that regulate contraction during cytokinesis, including ECT2, MgcRacGap, Anillin, and RHOA. In addition, depletion of YAP increased the phosphorylation of myosin light chain, which would be expected to activate the contractile activity of myosin II, the molecular motor involved in cytokinesis. The polarity scaffold protein PATJ coprecipitated with YAP and colocalized with YAP at the cytokinesis midbody, and knockdown of PATJ phenocopied the cytokinetic defects and spindle orientation alterations induced by either YAP depletion or expression of a nonphosphorylatable YAP mutant. Together, these results reveal an unanticipated role for YAP in the proper organization of the cytokinesis machinery during mitosis through interaction with the polarity protein PATJ. SN - 1937-9145 UR - https://www.unboundmedicine.com/medline/citation/26933062/Cytokinesis_involves_a_nontranscriptional_function_of_the_Hippo_pathway_effector_YAP_ L2 - http://stke.sciencemag.org/cgi/pmidlookup?view=long&pmid=26933062 DB - PRIME DP - Unbound Medicine ER -