Hippo Signal Transduction Mechanisms in T Cell Immunity

Antoine Bouchard; Mariko Witalis; Jinsam Chang; Vincent Panneton; Joanna Li; Yasser Bouklouch; Woong-Kyung Suh

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자료유형: 학술저널

저자정보: Antoine Bouchard (Institut de Recherches Cliniques de Montréal (IRCM)) Mariko Witalis (Institut de Recherches Cliniques de Montréal (IRCM)) Jinsam Chang (Institut de Recherches Cliniques de Montréal (IRCM)) Vincent Panneton (Institut de Recherches Cliniques de Montréal (IRCM)) Joanna Li (Institut de Recherches Cliniques de Montréal (IRCM)) Yasser Bouklouch (Institut de Recherches Cliniques de Montréal (IRCM)) Woong-Kyung Suh (Institut de Recherches Cliniques de Montréal (IRCM))

저널정보: 대한면역학회 Immune Network Immune Network Vol.20 No.5

발행연도: 2020.10

수록면: 1 - 13 (13page)

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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 coactivator 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.

#Hippo #Signal transduction #T cells

참고문헌 (65)

참고문헌 신청

Meng Z / 2016 / Mechanisms of Hippo pathway regulation / Genes Dev 30:1~17

Zhou D / 2009 / Mst1 and Mst2 maintain hepatocyte quiescence and suppress hepatocellular carcinoma development through inactivation of the Yap1 oncogene / Cancer Cell 16:425~438

Lu L / 2010 / Hippo signaling is a potent in vivo growth and tumor suppressor pathway in the mammalian liver / Proc Natl Acad Sci U S A 107:1437~1442

Song H / 2010 / Mammalian Mst1 and Mst2 kinases play essential roles in organ size control and tumor suppression / Proc Natl Acad Sci U S A 107:1431~1436

Chen X / 2020 / Molecular mechanism of Hippo-YAP1/TAZ pathway in heart development, disease, and regeneration / Front Physiol 11:389

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