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Hippo Signal Transduction Mechanisms in T Cell Immunity

Immune Network 2020년 20권 5호 p.36 ~ 36
Bouchard Antoine, Witalis Mariko, 장진삼, Panneton Vincent, Li Joanna, Bouklouch Yasser, 서웅경,
소속 상세정보
 ( Bouchard Antoine ) - Institut de Recherches Cliniques de Montreal
 ( Witalis Mariko ) - Institut de Recherches Cliniques de Montreal
장진삼 ( Chang Jin-Sam ) - Institut de Recherches Cliniques de Montreal
 ( Panneton Vincent ) - Institut de Recherches Cliniques de Montreal
 ( Li Joanna ) - Institut de Recherches Cliniques de Montreal
 ( Bouklouch Yasser ) - Institut de Recherches Cliniques de Montreal
서웅경 ( Suh Woong-Kyung ) - Institut de Recherches Cliniques de Montreal

Abstract


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.

키워드

Hippo; Signal transduction; T cells

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