Role of the Hippo pathway and mechanisms for controlling cellular localization of YAP/TAZ

FEBS J. 2022 Oct;289(19):5798-5818. doi: 10.1111/febs.16091. Epub 2021 Jul 13.

Abstract

The Hippo pathway is a crucial signaling mechanism that inhibits the growth of cells and organs during development and in disease. When the Hippo pathway is activated, YAP/TAZ transcriptional coactivators are phosphorylated by upstream kinases, preventing nuclear localization of YAP/TAZ. However, when the Hippo pathway is inhibited, YAP/TAZ localize mainly in the nucleus and induce the expression of target genes related to cell proliferation. Abnormal proliferation of cells is one of the hallmarks of cancer initiation, and activation of Hippo pathway dampens such cell proliferation. Various types of diseases including cancer can occur due to the dysregulation of the Hippo pathway. Therefore, a better understanding of the Hippo pathway signaling mechanisms, and in particular how YAP/TAZ exist in the nucleus, may lead to the identification of new therapeutic targets for treating cancer and other diseases. In this review, we summarize the overall Hippo pathway and discuss mechanisms related to nuclear localization of YAP/TAZ.

Keywords: Hippo pathway; TEAD; YAP/TAZ; cancer; nuclear-cytoplasmic shuttling.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Hippo Signaling Pathway
  • Humans
  • Neoplasms* / drug therapy
  • Protein Serine-Threonine Kinases* / genetics
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Trans-Activators
  • Transcription Factors
  • Protein Serine-Threonine Kinases