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Angiomotin is a novel Hippo pathway component that inhibits YAP oncoprotein
- Source :
- Genesdevelopment. 25(1)
- Publication Year :
- 2011
-
Abstract
- The Yes-associated protein (YAP) is a transcription coactivator that plays a crucial role in organ size control by promoting cell proliferation and inhibiting apoptosis. The Hippo tumor suppressor pathway inhibits YAP through phosphorylation-induced cytoplasmic retention and degradation. Here we report a novel mechanism of YAP regulation by angiomotin (AMOT) family proteins via a direct interaction. Knockdown of AMOT family protein AMOTL2 in polarized Madin-Darby canine kidney (MDCK) cells leads to YAP activation, as indicated by decreased YAP tight junction localization, attenuated YAP phosphorylation, accumulation of nuclear YAP, and induction of YAP target gene expression. Transcriptional coactivator with PDZ-binding motif (TAZ), the YAP paralog, is also regulated by AMOT in a similar fashion. Furthermore, AMOTL2 knockdown results in loss of cell contact inhibition in a manner dependent on the functions of YAP and TAZ. Our results indicate a potential tumor-suppressing role of AMOT family proteins as components of the Hippo pathway, and demonstrate a novel mechanism of YAP and TAZ inhibition by AMOT-mediated tight junction localization. These observations provide a potential link between the Hippo pathway and cell contact inhibition.
- Subjects :
- Cell signaling
Cell Cycle Proteins
Biology
Protein Serine-Threonine Kinases
Epithelium
Cell Line
Mice
Dogs
Genetics
Animals
Humans
Nuclear protein
Phosphorylation
Transcription factor
Hippo signaling pathway
HEK 293 cells
Microfilament Proteins
Membrane Proteins
Nuclear Proteins
Angiomotin
Transport protein
Cell biology
Protein Transport
Cell Transformation, Neoplastic
HEK293 Cells
Angiomotins
Gene Expression Regulation
Transcription Coactivator
Gene Knockdown Techniques
Intercellular Signaling Peptides and Proteins
Developmental Biology
HeLa Cells
Transcription Factors
Research Paper
Subjects
Details
- ISSN :
- 15495477
- Volume :
- 25
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Genesdevelopment
- Accession number :
- edsair.doi.dedup.....61ba1cc6e9fe0ac2bf5a81dda638abd7