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PLoS One. 2012;7(4):e35735. doi: 10.1371/journal.pone.0035735. Epub 2012 Apr 27.

YAP1 recruits c-Abl to protect angiomotin-like 1 from Nedd4-mediated degradation.

Author information

1
Renal Division, University Hospital Freiburg, Freiburg, Germany.

Abstract

BACKGROUND:

Tissue development and organ growth require constant remodeling of cell-cell contacts formed between epithelial cells. The Hippo signaling cascade curtails organ growth by excluding the transcriptional co-activator Yes Associated Protein 1 (YAP1) from the nucleus. Angiomotin family members recruit YAP1 to tight junctions [1], but whether YAP1 plays a specific role outside of the nucleus is currently unknown.

METHODOLOGY/PRINCIPAL FINDINGS:

The present study demonstrates that the E3 ubiquitin ligase Nedd4.2 targets Angiomotin-like 1 (AMOTL1), a family member that promotes the formation of epithelial tight junctions, for ubiquitin-dependent degradation. Unexpectedly, YAP1 antagonizes the function of Nedd4.2, and protects AMOTL1 against Nedd4.2-mediated degradation. YAP1 recruits c-Abl, a tyrosine kinase that binds and phosphorylates Nedd4.2 on tyrosine residues, thereby modifying its ubiquitin-ligase activity.

CONCLUSIONS/SIGNIFICANCE:

Our results uncover a novel function for cytoplasmic YAP1. YAP1 recruits c-Abl to protect AMOTL1 against Nedd4.2-mediated degradation. Thus, YAP1, excluded from the nucleus, contributes to the maintenance of tight junctions.

PMID:
22558212
PMCID:
PMC3338797
DOI:
10.1371/journal.pone.0035735
[Indexed for MEDLINE]
Free PMC Article

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