TAZ as a novel enhancer of MyoD‐mediated myogenic differentiation

Abstract

Myoblast differentiation is indispensable for skeletal muscle formation and is governed by the precisely coordinated regulation of a series of transcription factors, including MyoD and myogenin, and transcriptional coregulators. TAZ (transcriptional coactivator with PDZ-binding motif) has been characterized as a modulator of mesenchymal stem cell differentiation into osteoblasts and adipocytes through its regulation of lineage-specific master transcription factors. In this study, we investigated whether TAZ affects myoblast differentiation, which is one of the differentiated lineages of mesenchymal stem cells. Ectopic overexpression of TAZ in myoblasts increases myogenic gene expression in a MyoD-dependent manner and hastens myofiber formation, whereas TAZ knockdown delays myogenic differentiation. In addition, enforced coexpression of TAZ and MyoD in fibroblasts accelerates MyoD-induced myogenic differentiation. TAZ physically interacts with MyoD through the WW domain and activates MyoD-dependent gene transcription. TAZ additionally enhances the interaction of MyoD with the myogenin gene promoter. These results strongly suggest that TAZ functions as a novel transcriptional modulator of myogenic differentiation by promoting MyoD-mediated myogenic gene expression.

Cellular micro-environments reveal defective mechanosensing responses and elevated YAP signaling in LMNA-mutated muscle precursors

“…YAP is expressed in almost all cell types including skeletal muscles (Jeong et al, 2010;Watt et al, 2010;Judson et al, 2012). Mechanical cues of the microenvironment, such as substrate stiffness and topographic features, are crucial regulators of YAP-TAZ pathway and this regulation takes place through the regulation of the actomyosin cytoskeletal system (Dupont et al, 2011;Mendez and Janmey, 2012).…”

“…YAP is a crucial member of the Hippo pathway, and is expressed in almost all cell types (Mendez and Janmey, 2012), including skeletal muscles (Jeong et al, 2010;Watt et al, 2010;Judson et al, 2012). Although YAP recapitulates some aspects of MKL1-SRF regulation, its regulation appears distinct and seems to take place through regulation of the actomyosin cytoskeletal network instead of the ratio between F-actin and G-actin (Mendez and Janmey, 2012).…”

Canonical Wnt signalling activates TAZ through PP1A during osteogenic differentiation

“…2,10 The interaction between TAZ and Runx2 stimulates Runx2-mediated gene transcription. Wnts are a family of secreted glycoproteins that are involved in the regulation of cell proliferation, differentiation, axis formation, organ development and tissue homeostasis.…”

“…TAZ interacts with several transcription factors including Runx2, PPARg, TEADS, TTF-1/Nkx2.1, Tbx5, Pax3, Smad2/3-4 complexes, MyoD and NFAT5. [1][2][3][4][5][6][7][8][9][10][11] This interaction regulates the transcription of target genes with diverse biological functions. For example, TAZ and its paralogue YAP interact with TEADs and stimulate their target genes, including CTGF and Cyr61, to promote cell proliferation and migration.…”

The Hippo Kinase Pathway: a master regulator of proliferation, development and differentiation

“…YAP and TAZ per se are not able to bind DNA, but they regulate gene targets expression (either by activation or repression) through interaction with transcription factors in a tissue and development specific manner. By now, several YAP and TAZ interacting proteins have been characterized among which some are able to sequester or post-transcritpionally modify YAP and TAZ (table2) Chen and Sudol, 1995;Espanel and Sudol, 2001;Howell et al, 2004;Hsu and Lawlor, 2011;Koontz et al, 2013;Mohler et al, 1999;Rosenbluh et al, 2012;Sudol, 1994;Tsutsumi et al, 2013), others are transcriptional regulators (table3) (Cui et al, 2003;Di Palma et al, 2009;Ferrigno et al, 2002;Hsu and Lawlor, 2011;Jeong et al, 2010;Kang et al, 2009;Murakami et al, 2005;Xiao et al, 2013;Yagi et al, 1999). All the components of the Hippo pathway, from the membrane associated proteins to the cytoplasmic kinase cascade to the final effectors YAP and TAZ, are characterized by specific protein-protein interaction domains, among which the most common are WW domain and the similar SH3 domain, able to bind short peptides that are prolinrich and often terminate with Tyrosine (Y), named PpxY motifs (Sudol and Hunter, 2000).…”