How does the Hippo signaling pathway work?
The Hippo pathway is involved in cell contact inhibition, and its activity is regulated at multiple levels: Mst1/2 and LATS1/2 are regulated by upstream molecules such as Merlin, KIBRA, RASSFs, and Ajuba; 14-3-3, α-catenin, AMOT, and ZO-2 retain YAP/TAZ in the cytoplasm, adherens junctions, or tight junctions by …
How do you activate the Hippo pathway?
Extensive studies have revealed a myriad of intrinsic and extrinsic signals that can activate the Hippo pathway, including cell–cell contact, stiffness of the extracellular matrix, stress signals, and cell polarity (reviewed in [2,11,32–34]).
What is YAP pathway?
The Hippo-YAP pathway relays diversified extracellular and intracellular signals, including cell density, cell polarity, mechanical cues, ligands of G-protein-coupled receptors, cellular energy status, and orchestrates cell proliferation, survival, apoptosis, and differentiation and stemness.
What is Taz in YAP Taz?
YAP/TAZ are primary sensors of the cell’s physical nature, as defined by cell structure, shape and polarity. YAP/TAZ activation also reflects the cell “social” behavior, including cell adhesion and the mechanical signals that the cell receives from tissue architecture and surrounding extracellular matrix (ECM).
Why is the Hippo pathway important?
The Hippo pathway is pervasively activated and has been well recognized to play critical roles in human cancer. The deregulation of Hippo signaling involved in cancer development, progression, and resistance to cancer treatment have been confirmed in several human cancers.
What does YAP phosphorylation do?
YAP is phosphorylated and inhibited by the Lats tumor suppressor, and this phosphorylation results in its association with 14–3–3 and cytoplasmic localization. This regulatory mechanism is utilized in YAP regulation by cell density and is likely conserved in Drosophila.
Where does the Hippo pathway occur?
“Hippo Signaling in the Liver Regulates Organ Size, Cell Fate, and Carcinogenesis”.
What is the Hippo YAP Taz tumor suppressor pathway?
The main function of the Hippo pathway is to prevent YAP and TAZ translocation to the nucleus where they induce the transcription of genes involved in cell proliferation, survival, and stem cell maintenance. Hippo signaling is thus a complex tumor suppressor, and its deregulation is a key feature in many cancers.
How is YAP activated?
Stimulation of PAR by agonist peptides activates YAP/TAZ by inducing dephosphorylation and nuclear localization. PAR1 acts through G12/13, Rho, Lats1/2, and YAP/TAZ to stimulate gene expression, cell migration, and cell invasion.
What is YKI protein?
yki encodes the Drosophila ortholog of yes-associated protein (YAP), a transcriptional coactivator in mammalian cells (Yagi, 1999; Strano, 2001; Vassilev, 2001). Yki is required for normal tissue growth and diap1 transcription and is phosphorylated and inactivated by Wts.
How do hippos maintain homeostasis?
Recently, emerging evidence showed that Hippo pathway plays an important role in the homeostasis maintenance through regulating the cell proliferation, progenitor renewal and differentiation, and stress-induced cell apoptosis. The current knowledge of the in vivo roles of Hippo pathway is briefly discussed below.