J 2021

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

VRBSKY, Jan, Vladimir VINARSKY, Ana Rubina PERESTRELO, Jorge Oliver DE LA CRUZ, Fabiana MARTINO et. al.

Basic information

Original name

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

Authors

VRBSKY, Jan (203 Czech Republic, guarantor), Vladimir VINARSKY (203 Czech Republic), Ana Rubina PERESTRELO, Jorge Oliver DE LA CRUZ, Fabiana MARTINO (380 Italy, belonging to the institution), Antonio POMPEIANO, Valerio IZZI, Ota HLINOMAZ (203 Czech Republic), Vladimír ROTREKL (203 Czech Republic, belonging to the institution), Marius SUDOL, Stefania PAGLIARI and Giancarlo FORTE (380 Italy)

Edition

Genomics, United States, Elsevier Science Inc, 2021, 0888-7543

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

20802 Bioremediation, diagnostic biotechnologies in environmental management

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 4.310

RIV identification code

RIV/00216224:14110/21:00124209

Organization unit

Faculty of Medicine

UT WoS

000661249200008

Keywords in English

YAP1 isoforms; Alternative splicing; Tissue-specific expression; Cardiac differentiation

Tags

Tags

International impact, Reviewed
Změněno: 17/2/2022 08:18, Mgr. Tereza Miškechová

Abstract

V originále

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.