Regulation of Hippo signaling by actin remodeling

Abstract

The Hippo signaling pathway controls nuclear accumulation and stability of the transcriptional coregulator YAP and its paralog TAZ. The activity of Hippo-YAP signaling is influenced not only by biochemical signals, but also by cell shape and mechanical tension transmitted through cell-cell junctions and cell-matrix adhesions. Data accumulated thus far indicates that the actin cytoskeleton is a key mediator of the regulation of Hippo-YAP signaling by means of a variety of biochemical and mechanical cues. In this review, we have outlined the role of actin dynamics and actin-associated proteins in the regulation of Hippo-YAP signaling. In addition, we discuss actin-mediated regulation of YAP/TAZ activity independent of the core Hippo kinases MST and LATS. Although our understanding of the link between Hippo-YAP signaling and the actin cytoskeleton is progressing rapidly, many open questions remain.

Transcription Profiles of Age-at-Maturity-Associated Genes Suggest Cell Fate Commitment Regulation as a Key Factor in the Atlantic Salmon Maturation Process

“…Yap can regulate its own activation via negative feedback loop by upregulating at least Arhgap18 and Arghap29 which suppress RhoA activity. Based on the results of the current study and Halder et al 2012;Kim et al 2013;Yu et al 2013;Karystinou et al 2015;Porazinski et al 2015;Qiao et al 2017;Seo and Kim 2018. Ã Correlation of vgll3a mRNA expression with that of arhgap6e and akap11a (positive), and yap1 (negative).°Correlation of akap11a mRNA expression with that of vgll3a (positive), and lats1a and yap1 (negative).…”

“…As completion of maturation in Atlantic salmon (Rowe et al 1991) and another salmon species (Silverstein et al 1998) is highly dependent on the level of fat storage, the expression status of vgll3 could determine whether to induce adipogenesis or not and, therefore, regulate the timing of maturation. One of the main known regulators of cell fate is the Hippo signaling pathway member YAP (yes associated protein), a transcriptional cofactor that regulates cell proliferation and differentiation based on its cellular location and actin fiber status (Wada et al 2011;Halder et al 2012;Seo and Kim 2018) (Figure 5). However, there are contradictory results regarding the role of YAP in cell differentiation decisions (Seo et al 2013;Deel et al 2015;Karystinou et al 2015;Deng et al 2016).…”

The YAP/TAZ Pathway in Osteogenesis and Bone Sarcoma Pathogenesis

“…It is thus not surprising that many key molecules of metastatic progression are themselves rarely mutated but activated by intrinsic and extrinsic signaling cues in response to perturbed tissue homeostasis. Among these molecules are the transcriptional receptor (NOTCH), wingless (WNT) and bone morphogenetic protein (BMP) [41]. YAP and TAZ subcellular localization, stability and activity are regulated by protein phosphorylation, negatively on serines 127 and 397 (YAP) and 89 and 311 (TAZ) and positively on tyrosine 357 (YAP) and 316 (TAZ) [42].…”

“…Initially, RAS homology family member A (RHOA) was identified as the critical regulator of YAP; however, among the RHO GTPases Rac family, small GTPase 1 (RAC1) and cell division cycle 42 (CDC42) were also found to be involved in its regulation [17,39,40]. In addition, there is crosstalk with various other signaling pathways, including NOTCH receptor (NOTCH), wingless (WNT) and bone morphogenetic protein (BMP) [41]. YAP and TAZ subcellular localization, stability and activity are regulated by protein phosphorylation, negatively on serines 127 and 397 (YAP) and 89 and 311 (TAZ) and positively on tyrosine 357 (YAP) and 316 (TAZ) [42].…”

Rho-mediated gene transcription promotes BRAF inhibitor resistance in de-differentiated melanoma cells

“…As a result of modulating the actin cytoskeleton, Rho regulates gene transcription. Rhoinduced F-actin polymerization allows for MRTF and YAP1 to translocate into the nucleus where they subsequently regulate gene transcription 5,26,27,33,39,44 represented as a stacked bar graph wherein the fraction of cells that have predominantly nuclear, pan-cellular, or cytosolic localization is plotted as a fraction of the total cells. C) MRTF and YAP1 signatures were predicted for human melanoma tumor pairs which had an increase in RhoA/C signature score from (Fig.…”