Related Experiment Video

Updated: Jun 3, 2026

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

Yap1 acts downstream of α-catenin to control epidermal proliferation

Karin Schlegelmilch1, Morvarid Mohseni, Oktay Kirak

  • 1Stem Cell Program, Children's Hospital, Boston, MA 02115, USA.

Cell
|March 8, 2011
PubMed

Insights

Yap1, a key Hippo pathway component, controls epidermal stem cell proliferation and tissue growth in mammalian skin. Alpha-catenin acts as a negative regulator, modulating Yap1 activity and contributing to "crowd control" mechanisms.

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Dermatology

Background:

  • Tissue-specific stem cell proliferation is tightly regulated for organ size determination during development and regeneration.
  • The molecular mechanisms governing this control, particularly in skin, are not fully understood.
  • The Hippo signaling pathway and its effector Yap1 are known regulators of cell proliferation and organ size in various contexts.

Purpose of the Study:

  • To investigate the role of Yap1, the transcriptional effector of the Hippo pathway, in skin biology.
  • To elucidate the molecular mechanisms by which Yap1 regulates epidermal stem cell proliferation and tissue expansion.
  • To identify upstream regulators of Yap1 in the context of skin homeostasis.

Main Methods:

  • Gain- and loss-of-function studies were employed to assess Yap1's role in epidermal stem cells.
  • Investigated the interaction of Yap1 with TEAD transcription factors.
  • Analyzed the regulatory role of α-catenin on Yap1 activity, including its phosphorylation and interactions with 14-3-3 and PP2A phosphatase.

Main Results:

  • Yap1 was identified as a critical modulator of epidermal stem cell proliferation and skin tissue expansion.
  • Yap1 exerts its function through interaction with TEAD transcription factors.
  • α-catenin was found to be an upstream negative regulator of Yap1, controlling its activity and phosphorylation status by modulating interactions with 14-3-3 and PP2A phosphatase.

Conclusions:

  • Yap1 is a key determinant of the proliferative capacity of epidermal stem cells in mammalian skin.
  • Yap1 acts as an important effector in a molecular circuitry that controls tissue size, akin to "crowd control".
  • α-catenin plays a significant role in regulating Yap1 activity, contributing to the sensing of cell density and tumor suppression in the skin.

More Related Videos

CUBIC Protocol Visualizes Protein Expression at Single Cell Resolution in Whole Mount Skin Preparations08:09

CUBIC Protocol Visualizes Protein Expression at Single Cell Resolution in Whole Mount Skin Preparations

Published on: August 4, 2016

All-optical Mechanobiology Interrogation of Yes-associated Protein in Human Cancer and Normal Cells using a Multi-functional System09:55

All-optical Mechanobiology Interrogation of Yes-associated Protein in Human Cancer and Normal Cells using a Multi-functional System

Published on: December 20, 2021

Related Concept Videos

Catenins01:23

Catenins

Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the adherens...
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
Mechanism of Lamellipodia Formation01:31

Mechanism of Lamellipodia Formation

Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...