Angiomotin-Like Protein 1 Controls Endothelial Polarity and Junction Stability During Sprouting Angiogenesis

Zheng, Yi; Vertuani, Simona; Nyström, Staffan; Audebert, Stéphane; Meijer, Inèz; Tegnebratt, Tetyana; Borg, Jean-Paul; Uhlén, Per; Majumdar, Årindam; Holmgren, Lars

doi:10.1161/circresaha.109.195156

Cited by 107 publications

(121 citation statements)

References 29 publications

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“…AMOTL1 shares ϳ60% homologous with AMOT and has an expression pattern similar to AMOT in endothelial cell (28). We showed that just like AMOTL1 and AMOTL2, AMOT also binds directly to YAP1 via the WW domain of YAP1 and the PY motifs located at the N terminus of AMOT (please see supplemental Fig.…”

Section: Discussionmentioning

confidence: 75%

Angiomotin-like Proteins Associate with and Negatively Regulate YAP1

Wang

Huang

Chen

2011

Journal of Biological Chemistry

233

254

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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.

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Section: Discussionmentioning

confidence: 75%

Angiomotin-like Proteins Associate with and Negatively Regulate YAP1

Wang

Huang

Chen

2011

Journal of Biological Chemistry

233

254

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“…Morpholinos, mRNA Synthesis, and Microinjection-Antisense morpholinos targeting different zebrafish Motin members were: amotMO1 (5Ј-CCACTGACACAACTACCACCA-AGTG-3Ј) (36), amotl1MO1 (5Ј-CCTCGATC TCCA-ACTGCAAATGTTC-3Ј) (37), and amotl2MO1 (5Ј-CTGAT-GATTC CTCTGCCGTTCTCAT-3Ј) (19). amotl2cMO1 (5Ј-TACTCTTGCCGTCTCCTTA GTAGTC-3Ј) was a control which was inverted from amotl2MO1 (19).…”

Section: Methodsmentioning

confidence: 99%

The Amotl2 Gene Inhibits Wnt/β-Catenin Signaling and Regulates Embryonic Development in Zebrafish

Wang

Zhang

et al. 2012

Journal of Biological Chemistry

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“…We have previously shown that each member has a distinct role in blood vessel formation in that Amot controls migration, AmotL1 junction formation and AmotL2 aortic lumen expansion [16][17][18] . Acting as a scaffold protein, AmotL2 and its related proteins associate and join together proteins involved in junction formation, apical polarity and actin cytoskeleton 19 .…”

mentioning

confidence: 99%

AmotL2 disrupts apical–basal cell polarity and promotes tumour invasion

et al. 2014

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The establishment and maintenance of apical-basal cell polarity is essential for the functionality of glandular epithelia. Cell polarity is often lost in advanced tumours correlating with acquisition of invasive and malignant properties. Despite extensive knowledge regarding the formation and maintenance of polarity, the mechanisms that deregulate polarity in metastasizing cells remain to be fully characterized. Here we show that AmotL2 expression correlates with loss of tissue architecture in tumours from human breast and colon cancer patients. We further show that hypoxic stress results in activation of c-Fos-dependent expression of AmotL2 leading to loss of polarity. c-Fos/hypoxia-induced p60 AmotL2 interacts with the Crb3 and Par3 polarity complexes retaining them in large vesicles and preventing them from reaching the apical membrane. The resulting loss of polarity potentiates the response to invasive cues in vitro and in vivo in mice. These data provide a molecular mechanism how hypoxic stress deregulates cell polarity during tumour progression.

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Angiomotin-Like Protein 1 Controls Endothelial Polarity and Junction Stability During Sprouting Angiogenesis

Cited by 107 publications

References 29 publications

Angiomotin-like Proteins Associate with and Negatively Regulate YAP1

Angiomotin-like Proteins Associate with and Negatively Regulate YAP1

The Amotl2 Gene Inhibits Wnt/β-Catenin Signaling and Regulates Embryonic Development in Zebrafish

AmotL2 disrupts apical–basal cell polarity and promotes tumour invasion

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