Angiomotin belongs to a novel protein family with conserved coiled-coil and PDZ binding domains

Bratt, Anders; Wilson, William J.; Troyanovsky, Boris; Aase, Karin; Kessler, Reto; Meir, Erwin G. Van; Holmgren, Lars

doi:10.1016/s0378-1119(02)00928-9

Cited by 134 publications

(154 citation statements)

References 23 publications

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“…The reported regulation of AmotL2 by hypoxia and its effect on cellular migration prompted us to analyse the expression pattern of AmotL2 in human cancer 15,[22][23][24] . AmotL2 protein expression was detected by immunohistochemical staining of paraffin-embedded sections from breast and colon cancer patients.…”

Section: Resultsmentioning

confidence: 99%

“…AAH11454; ref. 15). Both breast and colon tumour tissues were negative for immunohistochemical staining using a p100 AmotL2-specific antibody ( Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

“…AmotL2 belongs to the Angiomotin (Amot) family of membrane-associated scaffold proteins and contains an aminoterminal glutamine-rich domain, coiled-coil repeats and a carboxy-terminal PDZ (for Psd-95 (postsynaptic protein), DlgA (Drosophila disc large tumour suppressor) and ZO1 (zona occludens))-binding domain that together structurally define the Amot family 15 . 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] .…”

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confidence: 99%

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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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Section: Resultsmentioning

confidence: 99%

“…AAH11454; ref. 15). Both breast and colon tumour tissues were negative for immunohistochemical staining using a p100 AmotL2-specific antibody ( Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

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confidence: 99%

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AmotL2 disrupts apical–basal cell polarity and promotes tumour invasion

et al. 2014

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“…AMOTL2 was identified as a novel member of the angiomotin family. 28 Angiomotin itself may promote angiogenesis by increasing cell motility. 29 The exact function of AMOTL2 and its involvement in regulation of cell motility, growth and survival, if any, remains to be established.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia induces p53-dependent transactivation and Fas/CD95-dependent apoptosis

et al. 2006

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p53 triggers apoptosis in response to cellular stress. We analyzed p53-dependent gene and protein expression in response to hypoxia using wild-type p53-carrying or p53 null HCT116 colon carcinoma cells. Hypoxia induced p53 protein levels and p53-dependent apoptosis in these cells. cDNA microarray analysis revealed that only a limited number of genes were regulated by p53 upon hypoxia. Most classical p53 target genes were not upregulated. However, we found that Fas/CD95 was significantly induced in response to hypoxia in a p53-dependent manner, along with several novel p53 target genes including ANXA1, DDIT3/ GADD153 (CHOP), SEL1L and SMURF1. Disruption of Fas/CD95 signalling using anti-Fas-blocking antibody or a caspase 8 inhibitor abrogated p53-induced apoptosis in response to hypoxia. We conclude that hypoxia triggers a p53-dependent gene expression pattern distinct from that induced by other stress agents and that Fas/CD95 is a critical regulator of p53-dependent apoptosis upon hypoxia. The tumor suppressor p53 regulates cellular processes such as cell cycle progression, DNA repair and apoptosis. 1 p53 is stabilized and activated in response to different types of cellular stress, for example, DNA damage, oncogenic signalling and hypoxia, and induces a biological response through transcriptional regulation of downstream target genes. The molecular mechanisms that dictate the decision of a cell to enter growth arrest or undergo apoptosis or both in response to p53 activation are only partially understood. Also, it remains unclear why different cell types display differential response to functional p53. The biological outcome of p53 activation presumably depends on several factors, including cellular context, cell type and type of stress agent. 1 It is plausible that p53 activates different specific and possibly overlapping set of target genes in response to different stress signals. Therefore, knowledge about the target genes and their regulation under different conditions is vital for the understanding of p53-mediated tumor suppression.Previous DNA microarray studies have allowed a global analysis of p53-dependent gene expression in response to p53 activation by various means. 2,3 These studies have indicated that several hundred genes are potentially regulated by p53. Moreover, in silico analysis of the human genome sequence has revealed that up to 4800 genes contain one or more potential p53 binding sites. 4,5 Thus, it is conceivable that a large number of genes are regulated by p53, although not necessarily in the same cell in response to the same stress signal. Microarray studies have so far relied on artificial cell systems for activation of p53, for example, the metallothionein promoter or expression of exogenous p53. In addition, the numbers of genes on the arrays used have been relatively low. Thus, further studies of p53-dependent gene expression based on activation of endogenous p53 in response to physiological cellular stress should provide more reliable information about p53-dependent stress respon...

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“…1 Here, we report the identification of angiomotin (AMOT) and angiomotin-like proteins as new YAP1-associated proteins. AMOT is a vascular angiogenesis-related protein, which was initially identified as an angiogenesis inhibitor angiostatin-binding protein through a yeast twohybrid screen (23,24). AMOT can induce endothelial cell migration and tubule formation, and therefore, it promotes angiogenesis (23,25).…”

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confidence: 99%

Angiomotin-like Proteins Associate with and Negatively Regulate YAP1

Wang

Huang

Chen

2011

Journal of Biological Chemistry

240

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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Angiomotin belongs to a novel protein family with conserved coiled-coil and PDZ binding domains

Cited by 134 publications

References 23 publications

AmotL2 disrupts apical–basal cell polarity and promotes tumour invasion

AmotL2 disrupts apical–basal cell polarity and promotes tumour invasion

Hypoxia induces p53-dependent transactivation and Fas/CD95-dependent apoptosis

Angiomotin-like Proteins Associate with and Negatively Regulate YAP1

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