YAP nuclear‐cytoplasmic translocation is regulated by mechanical signaling, protein modification, and metabolism

Abstract

Nuclear‐cytoplasmic transport is necessary for the biological function of nuclear proteins. The mechanism underlying this process is very complex and has been a subject of intense research. Yes‐associated protein (YAP), a Hippo signaling pathway effector, localizes to both the cytoplasm and the nucleus and can influence cell proliferation, stem cell status, and tissue homeostasis. Recent studies have focused on the significance of YAP distribution between the nucleus and the cytoplasm in disease, but it remains unclear how this dynamic process is regulated. In this review, we discuss YAP nuclear‐cytoplasmic transport under different physiological and pathological conditions in terms of mechanical signaling, protein modification, and metabolism. Understanding the mechanisms underlying nuclear‐cytoplasmic YAP transport mechanism under different physiological and pathological conditions may help identify important targets for disease treatment.

Topological defects of integer charge in cell monolayers

“…YAP is mechanosensitive and translocates from the nucleus to the cytoplasm when cells are subjected to mechanical strain such as compression. 29,30 In fibroblasts, near +1 defects, YAP is more localized in the cell cytoplasm, suggesting the presence of mechanical strain. On the other hand, cells near À1 defects have YAP localized in nuclei.…”

Radial extracorporeal shockwave promotes subchondral bone stem/progenitor cell self-renewal by activating YAP/TAZ and facilitates cartilage repair in vivo

“…However, the concrete mechanisms of r-ESW in vivo still need to be explored. YAP/TAZ, the effector of the Hippo pathway, has been demonstrated to play pivotal roles in mechanomeditated stem cell plasticity and stemness regulation during tissue regeneration [40,41]. Moreover, numerous studies have suggested that YAP protein activity could be regulated directly by mechanical cues from both the microenvironment, such as extracellular matrix stiffness, and other extraneous stimulation independent of the Hippo pathway [42,43].…”

“…Moreover, numerous studies have suggested that YAP protein activity could be regulated directly by mechanical cues from both the microenvironment, such as extracellular matrix stiffness, and other extraneous stimulation independent of the Hippo pathway [42,43]. Notably, mechanical stimuli could influence YAP nuclear-cytoplasmic distribution and in turn modulate cell biological function [40,44]. DuPont et al identified YAP/TAZ as sensors and effector proteins of mechanical cues perceived from extracellular rigidity [45].…”

“…DuPont et al identified YAP/TAZ as sensors and effector proteins of mechanical cues perceived from extracellular rigidity [45]. Additionally, YAP/TAZ also responds to different kinds of mechanical stresses, including shearing, compressing, or pulling [40]. Extracorporeal shockwaves, a unique physical stimulus composed of compression, tension, and shear forces, are transient pressure disturbances that propagate rapidly in three-dimensional space.…”

An Updated Understanding of the Role of YAP in Driving Oncogenic Responses

“…Overall, we can mention at least four large groups of upstream pathways that regulate YAP nuclear localization and function [ 33 ], subdivided into: (i) mechanotransduction; (ii) polarity and tight junction proteins; (iii) the cadherin-catenin complex; and (iv) soluble growth factors.…”