Key Processes in Health and Disease Regulated by the Hippo Pathway

Dear Colleagues,

The Hippo pathway is known to participate in the genetic program that dictates one pre-defined size of an adult organ, in the presence of the correct nutrient availability. Organ size relies on a delicate balance between cell proliferation, apoptosis, and cell self-renewal events, all features controlled by the Hippo pathway. If, on one hand, the Hippo cascade seems to participate in all stages of development from fetus to adult life in healthy individuals, at the same time and in the presence of either mutations or altered expression in genes, as an aberrant function of proteins of this signaling cascade, it may be associated to disorders concerning cancer, cardiovascular pathologies, and inherited familial diseases.

The key components of this pathway may be summarized in two complex modules: the first one based on serine–threonine kinase activity and the second involving co-transcriptional effectors. Proteins with kinase activities are MST1 and MST2, and LATS1 and LATS2. Here, mutations led to uncontrolled overgrowth of epithelial tissues. Domains in the carboxyl terminus in MSTs mediate heterodimer formations with SAV1, crucial for LATS1/2 phosphorylation. On the other hand, transcriptional co-activators are represented by the yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ, also known as WWTR1). When the kinase module is inactive, YAP and TAZ are not phosphorylated and translocate from the cytosol to the nucleus where they induce the expression of several genes involved in cancer signaling, being considered as potent oncogenes, but also in cardiac remodeling in many types of cardiomyopathies. When MST1/2 and LATS1/2 are active and phosphorylated, in turn, they mediate the phosphorylation of YAP and TAZ which remain in the cytosol where they may be degraded by the proteasome or assume additional functions.

In this Research Topic, we call for articles and reviews that are able to summarize, in an original and innovative view, the latest findings and molecular insights on the involvement of proteins, interactors, and upstream regulators in health and disease.

Dr. Giampaolo Morciano
Guest Editor

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