Hippo Signal Transduction Mechanisms in T Cell Immunity.

Autor:	Bouchard A; Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC H2W 1R7, Canada.; Molecular Biology Program, Department of Medicine, University of Montreal, Montreal, QC H3T 1J4, Canada., Witalis M; Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC H2W 1R7, Canada.; Molecular Biology Program, Department of Medicine, University of Montreal, Montreal, QC H3T 1J4, Canada., Chang J; Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC H2W 1R7, Canada.; Molecular Biology Program, Department of Medicine, University of Montreal, Montreal, QC H3T 1J4, Canada., Panneton V; Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC H2W 1R7, Canada.; Department of Microbiology, Infectiology, and Immunology, University of Montreal, Montreal, QC H3T 1J4, Canada., Li J; Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC H2W 1R7, Canada.; Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 0G4, Canada., Bouklouch Y; Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC H2W 1R7, Canada., Suh WK; Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC H2W 1R7, Canada.; Molecular Biology Program, Department of Medicine, University of Montreal, Montreal, QC H3T 1J4, Canada.; Department of Microbiology, Infectiology, and Immunology, University of Montreal, Montreal, QC H3T 1J4, Canada.; Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 0G4, Canada.
Jazyk:	angličtina
Zdroj:	Immune network [Immune Netw] 2020 Oct 19; Vol. 20 (5), pp. e36. Date of Electronic Publication: 2020 Oct 19 (Print Publication: 2020).
DOI:	10.4110/in.2020.20.e36
Abstrakt:	Hippo signaling pathways are evolutionarily conserved signal transduction mechanisms mainly involved in organ size control, tissue regeneration, and tumor suppression. However, in mammals, the primary role of Hippo signaling seems to be regulation of immunity. As such, humans with null mutations in STK4 (mammalian homologue of Drosophila Hippo ; also known as MST1 ) suffer from recurrent infections and autoimmune symptoms. Although dysregulated T cell homeostasis and functions have been identified in MST1-deficient human patients and mouse models, detailed cellular and molecular bases of the immune dysfunction remain to be elucidated. Although the canonical Hippo signaling pathway involves transcriptional co-activator Yes-associated protein (YAP) or transcriptional coactivator with PDZ motif (TAZ), the major Hippo downstream signaling pathways in T cells are YAP/TAZ-independent and they widely differ between T cell subsets. Here we will review Hippo signaling mechanisms in T cell immunity and describe their implications for immune defects found in MST1-deficient patients and animals. Further, we propose that mutual inhibition of Mst and Akt kinases and their opposing roles on the stability and function of forkhead box O and β-catenin may explain various immune defects discovered in mutant mice lacking Hippo signaling components. Understanding these diverse Hippo signaling pathways and their interplay with other evolutionarily-conserved signaling components in T cells may uncover molecular targets relevant to vaccination, autoimmune diseases, and cancer immunotherapies. Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interest. (Copyright © 2020. The Korean Association of Immunologists.)
Databáze:	MEDLINE
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