Evidence for discrete modes of YAP1 signaling via mRNA splice isoforms in development and diseases.

Autor: Vrbský J; International Clinical Research Center (ICRC), St Anne's University Hospital, CZ-65691 Brno, Czech Republic. Electronic address: jan.vrbsky@fnusa.cz., Vinarský V; International Clinical Research Center (ICRC), St Anne's University Hospital, CZ-65691 Brno, Czech Republic; Competence Center for Mechanobiology in Regenerative Medicine, INTERREG ATCZ133, CZ-62500 Brno, Czech Republic., Perestrelo AR; International Clinical Research Center (ICRC), St Anne's University Hospital, CZ-65691 Brno, Czech Republic., De La Cruz JO; International Clinical Research Center (ICRC), St Anne's University Hospital, CZ-65691 Brno, Czech Republic; Competence Center for Mechanobiology in Regenerative Medicine, INTERREG ATCZ133, CZ-62500 Brno, Czech Republic., Martino F; International Clinical Research Center (ICRC), St Anne's University Hospital, CZ-65691 Brno, Czech Republic; Competence Center for Mechanobiology in Regenerative Medicine, INTERREG ATCZ133, CZ-62500 Brno, Czech Republic; Department of Biology, Masaryk University, CZ-62500 Brno, Czech Republic., Pompeiano A; International Clinical Research Center (ICRC), St Anne's University Hospital, CZ-65691 Brno, Czech Republic., Izzi V; University of Oulu, FI-90014 Oulu, Finland; Finnish Cancer Institute, 00130 Helsinki, Finland., Hlinomaz O; International Clinical Research Center (ICRC), St Anne's University Hospital, CZ-65691 Brno, Czech Republic., Rotrekl V; Department of Biology, Masaryk University, CZ-62500 Brno, Czech Republic., Sudol M; Department of Physiology, Yong Loo Li School of Medicine, Block MD9, 2 Medical Drive #04-01, 117597, Singapore; Mechanobiology Institute, T-Lab, 5A Engineering Drive 1, 117411, Singapore; Department of Medicine, Icahn School of Medicine at Mount Sinai, NY, New York 10029, United States of America., Pagliari S; International Clinical Research Center (ICRC), St Anne's University Hospital, CZ-65691 Brno, Czech Republic., Forte G; International Clinical Research Center (ICRC), St Anne's University Hospital, CZ-65691 Brno, Czech Republic; Competence Center for Mechanobiology in Regenerative Medicine, INTERREG ATCZ133, CZ-62500 Brno, Czech Republic. Electronic address: giancarlo.forte@fnusa.cz.
Jazyk: angličtina
Zdroj: Genomics [Genomics] 2021 May; Vol. 113 (3), pp. 1349-1365. Date of Electronic Publication: 2021 Mar 11.
DOI: 10.1016/j.ygeno.2021.03.009
Abstrakt: Yes-associated protein 1 (YAP1) is a transcriptional co-activator downstream of Hippo pathway. The pathway exerts crucial roles in organogenesis and its dysregulation is associated with the spreading of different cancer types. YAP1 gene encodes for multiple protein isoforms, whose specific functions are not well defined. We demonstrate the splicing of isoform-specific mRNAs is controlled in a stage- and tissue-specific fashion. We designed expression vectors encoding for the most-represented isoforms of YAP1 with either one or two WW domains and studied their specific signaling activities in YAP1 knock-out cell lines. YAP1 isoforms display both common and unique functions and activate distinct transcriptional programs, as the result of their unique protein interactomes. By generating TEAD-based transcriptional reporter cell lines, we demonstrate individual YAP1 isoforms display unique effects on cell proliferation and differentiation. Finally, we illustrate the complexity of the regulation of Hippo-YAP1 effector in physiological and in pathological conditions of the heart.
(Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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