A feedback loop between plakophilin 4 and YAP signaling regulates keratinocyte differentiation.

ABSTRACT: The Hippo signaling pathway is an important regulator of organ growth and differentiation, and its deregulation contributes to the development of cancer. The activity of its downstream targets YAP/TAZ depends on adherens junctions. Plakophilin 4 (PKP4) is a cell-type specific adherens junction protein expressed in the proliferating cells of the epidermis. Here, we show that PKP4 diminishes proliferation as well as differentiation. Depletion of PKP4 increased proliferation but at the same time induced premature epidermal differentiation. PKP4 interacted with several Hippo pathway components, including the transcriptional co-activators YAP/TAZ, and promoted nuclear YAP localization and target gene expression. In differentiated keratinocytes, PKP4 recruited LATS and YAP to cell junctions wher

SUBMITTER: Muller L 

PROVIDER: S-EPMC11402648 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature