Transcriptional Factor Aryl Hydrocarbon Receptor (Ahr) Controls Cardiovascular and Respiratory Functions by Regulating the Expression of the Vav3 Proto-oncogene

Sauzeau, Vincent; Carvajal-González, José María; Riolobos, Adelaida Sánchez; Sevilla, María A.; Menacho‐Marquez, Mauricio; Román, Ángel; Abad, Antonio; Montero, María J.; Fernandez-Salguero, Pedro; Bustelo, Xosé R.

doi:10.1074/jbc.m110.187534

Cited by 57 publications

(37 citation statements)

References 68 publications

(86 reference statements)

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“…Consistent with this idea, we have reported previously that the expression of the Vav3 gene, but not that of other Vav family genes, depends on the abundance of the transcription factor Ahr (aryl hydrocarbon receptor) in both mouse tissues and primary cells (36,37). Consistent with this, Vav3 −/− and Ahr −/− mice display similar nervous system and cardiovascular defects (37). Additional experiments will be required to address this issue.…”

Section: Discussionsupporting

confidence: 71%

The Rho Exchange Factors Vav2 and Vav3 Control a Lung Metastasis–Specific Transcriptional Program in Breast Cancer Cells

et al. 2012

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The guanosine triphosphatases of the Rho and Rac subfamilies regulate protumorigenic pathways and are activated by guanine nucleotide exchange factors (Rho GEFs), which could be potential targets for anticancer therapies. We report that two Rho GEFs, Vav2 and Vav3, play synergistic roles in breast cancer by sustaining tumor growth, neoangiogenesis, and many of the steps involved in lung-specific metastasis. The involvement of Vav proteins in these processes did not correlate with Rac1 and RhoA activity or cell migration, implying the presence of additional biological programs. Microarray analyses revealed that Vav2 and Vav3 controlled a vast transcriptional program in breast cancer cells through mechanisms that were shared between the two proteins, isoform-specific or synergistic. Furthermore, the abundance of Vav-regulated transcripts was modulated by Rac1-dependent and Rac1-independent pathways. This transcriptome encoded therapeutically targetable proteins that played nonredundant roles in primary tumorigenesis and lung-specific metastasis, such as integrin-linked kinase (Ilk), the transforming growth factor-β family ligand inhibin βA, cyclooxygenase-2, and the epithelial cell adhesion molecule Tacstd2. It also contained gene signatures that predicted disease outcome in breast cancer patients. These results identify possible targets for treating breast cancer and lung metastases and provide a potential diagnostic tool for clinical use.

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Section: Discussionsupporting

confidence: 71%

The Rho Exchange Factors Vav2 and Vav3 Control a Lung Metastasis–Specific Transcriptional Program in Breast Cancer Cells

et al. 2012

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“…Although the functions of Vav proteins in the nervous system are far from clear, several studies have found critical roles for Vav family members in nervous system function. For example, Vav proteins have been shown to be important for axonal development (Cowan et al 2005;Malartre et al 2010;Sauzeau et al 2010a;Fernandez-Espartero et al 2013), synaptic plasticity (Hale et al 2011), and negative regulation of sympathetic nervous system activity (Sauzeau et al 2006(Sauzeau et al , 2007(Sauzeau et al , 2010b(Sauzeau et al , 2011Zhu et al 2015). Moreover, Vav3 has been identified as a candidate schizophrenia gene (Ikeda et al 2011;Aleksic et al 2013).…”

Section: Discussionmentioning

confidence: 99%

A Conserved GEF for Rho-Family GTPases Acts in an EGF Signaling Pathway to Promote Sleep-like Quiescence inCaenorhabditis elegans

et al. 2016

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Sleep is evolutionarily conserved and required for organism homeostasis and survival. Despite this importance, the molecular and cellular mechanisms underlying sleep are not well understood. Caenorhabditis elegans exhibits sleep-like behavioral quiescence and thus provides a valuable, simple model system for the study of cellular and molecular regulators of this process. In C. elegans, epidermal growth factor receptor (EGFR) signaling is required in the neurosecretory neuron ALA to promote sleep-like behavioral quiescence after cellular stress. We describe a novel role for VAV-1, a conserved guanine nucleotide exchange factor (GEF) for Rho-family GTPases, in regulation of sleep-like behavioral quiescence. VAV-1, in a GEF-dependent manner, acts in ALA to suppress locomotion and feeding during sleep-like behavioral quiescence in response to cellular stress. Additionally, VAV-1 activity is required for EGF-induced sleep-like quiescence and normal levels of EGFR and secretory dense core vesicles in ALA. Importantly, the role of VAV-1 in promoting cellular stress-induced behavioral quiescence is vital for organism health because VAV-1 is required for normal survival after cellular stress.KEYWORDS behavioral quiescence; Caenorhabditis elegans; sleep; Vav D ESPITE being a subject of formal study for over 150 years, sleep is not clearly understood. Moreover, various explanations for the functional role of sleep have been proposed, such as allowing "recharging" of cells following high metabolic activity (Benington and Heller 1995;Tu and McKnight 2006;Scharf et al. 2008) and remodeling of synapses built during wakefulness (Tononi and Cirelli 2006). Yet sleep problems have a significant impact on human health and are a leading reason for seeking medical attention (Mahowald and Schenck 2005). Therefore, there is a great need for understanding the cellular and molecular mechanisms that regulate sleep-wake cycles.Simple model organisms such as Caenorhabditis elegans have the potential to provide valuable information regarding sleep regulation. C. elegans is known for its easily manipulated genetics, small nervous system with mapped neuronal connectivity, stereotypical behaviors, and the ability to be studied efficiently in large numbers. Numerous studies have shown that C. elegans lethargus, a restful period that occurs before each molt of the cuticle during larval development, is neuronally regulated and likely orthologous to sleep in mammals (Van Buskirk and Sternberg 2007;Raizen et al. 2008;Van Buskirk and Sternberg 2010;Choi et al. 2013;Iwanir et al. 2013;Turek et al. 2013;Cho and Sternberg 2014;Singh et al. 2014). Lethargus quiescence in C. elegans shares several characteristics with mammalian sleep: inactivity (decreased locomotion and cessation of pharyngeal pumping, or feeding), a specific posture, reduced response to aversive stimuli, and rapid reversibility (Cassada and Russell 1975;Raizen et al. 2008;Schwarz et al. 2012;Iwanir et al. 2013;Cho and Sternberg 2014). In addition, lethargus quiescence is under ...

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“…Ectopic activation of these pathways can cause severe damage to organisms and their ecosystem by altering reproduction, hormonal and/or circulatory systems [73][74][75] as well as they have been associated with carcinogenic and mutagenic effects [76][77][78]. Biological assays allow to complete sunscreens degradation analysis by measuring biological activity of the whole sample taking into account unknown metabolites and potential synergistic effects.…”

Section: Biological Activity Evolution Profile Through the Biodegradamentioning

confidence: 99%

UV Filters Biodegradation by Fungi, Metabolites Identification and Biological Activity Assessment

Badia-Fabregat

Caminal

Vicent

et al. 2012

The Handbook of Environmental Chemistry

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Organic UV filters used in cosmetics and sunlight protection of materials are considered emerging contaminants. These xenobiotic compounds occur in the environment in relevant concentrations and display critical properties such as environmental persistence and bioaccumulation. They enter the environment mainly through the liquid effluent of wastewater treatment plants (WWTPs), but, due to their high hydrophobicity, they are also adsorbed in WWTP sludge, that is, eventually spread on agricultural fields as fertilizer. The treatment of WWTP sludge with the white-rot fungi Trametes versicolor has emerged as a feasible alternative to current conventional treatment processes to degrade them in a range from 87% in the case of 3-(4 0 -methylbenzylidene) camphor (4-MBC) to 100% of benzophenone-3 (BP3) and its metabolite 4,4 0 -dihydroxybenzophenone (4DHB). When treating the sewage sludge to remove sunscreens content, it is crucial to establish the biological activity profile along the process. metabolites possessed significant oestrogenic activity at the produced concentrations. These results demonstrate the suitability of fungi to degrade sunscreen agents and eliminate their oestrogenic activity.

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Transcriptional Factor Aryl Hydrocarbon Receptor (Ahr) Controls Cardiovascular and Respiratory Functions by Regulating the Expression of the Vav3 Proto-oncogene

Abstract: Aryl hydrocarbon receptor (Ahr) is a transcriptional factor involved in detoxification responses to pollutants and in intrinsic

Cited by 57 publications

References 68 publications

The Rho Exchange Factors Vav2 and Vav3 Control a Lung Metastasis–Specific Transcriptional Program in Breast Cancer Cells

The Rho Exchange Factors Vav2 and Vav3 Control a Lung Metastasis–Specific Transcriptional Program in Breast Cancer Cells

A Conserved GEF for Rho-Family GTPases Acts in an EGF Signaling Pathway to Promote Sleep-like Quiescence inCaenorhabditis elegans

UV Filters Biodegradation by Fungi, Metabolites Identification and Biological Activity Assessment

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