TY - JOUR
T1 - Angiomotin-like proteins associate with and negatively regulate YAP1
AU - Wang, Wenqi
AU - Huang, Jun
AU - Chen, Junjie
PY - 2011/2/11
Y1 - 2011/2/11
N2 - In both Drosophila and mammalian systems, the Hippo pathway plays an important role in controlling organ size, mainly through its ability to regulate cell proliferation and apoptosis. The key component in the Hippo pathway is the Yes-associated protein YAP1, which localizes in nucleus, functions as a transcriptional coactivator, and regulates the expression of several proliferation- and apoptosis-related genes. The Hippo pathway negatively regulates YAP1 transcriptional activity by modulating its nuclear-cytoplasmic localization in a phosphorylation-dependent manner. Here, we describe the identification of several new PY motif-containing proteins, including angiomotin-like protein 1 (AMOTL1) and 2 (AMOTL2), as YAP1-associated proteins. We demonstrate that AMOTL1 and AMOTL2 can regulate YAP1 cytoplasm-tonucleus translocation through direct protein-protein interaction, which can occur independent of YAP1 phosphorylation status. Moreover, down-regulation of AMOTL2 in MCF10A cells promotes epithelial-mesenchymal transition, a phenotype that is also observed in MCF10A cells with YAP1 overexpression. Together, these data support a new mechanism for YAP1 regulation, which is mediated via its direct interactions with angiomotin-like proteins.
AB - In both Drosophila and mammalian systems, the Hippo pathway plays an important role in controlling organ size, mainly through its ability to regulate cell proliferation and apoptosis. The key component in the Hippo pathway is the Yes-associated protein YAP1, which localizes in nucleus, functions as a transcriptional coactivator, and regulates the expression of several proliferation- and apoptosis-related genes. The Hippo pathway negatively regulates YAP1 transcriptional activity by modulating its nuclear-cytoplasmic localization in a phosphorylation-dependent manner. Here, we describe the identification of several new PY motif-containing proteins, including angiomotin-like protein 1 (AMOTL1) and 2 (AMOTL2), as YAP1-associated proteins. We demonstrate that AMOTL1 and AMOTL2 can regulate YAP1 cytoplasm-tonucleus translocation through direct protein-protein interaction, which can occur independent of YAP1 phosphorylation status. Moreover, down-regulation of AMOTL2 in MCF10A cells promotes epithelial-mesenchymal transition, a phenotype that is also observed in MCF10A cells with YAP1 overexpression. Together, these data support a new mechanism for YAP1 regulation, which is mediated via its direct interactions with angiomotin-like proteins.
UR - http://www.scopus.com/inward/record.url?scp=79953010044&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79953010044&partnerID=8YFLogxK
U2 - 10.1074/jbc.C110.205401
DO - 10.1074/jbc.C110.205401
M3 - Article
C2 - 21187284
AN - SCOPUS:79953010044
SN - 0021-9258
VL - 286
SP - 4364
EP - 4370
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 6
ER -