Notch and Mef2 synergize to promote proliferation and metastasis through JNK signal activation in<i>Drosophila</i>

Pallavi, SK; Ho, Diana M.; Hicks, Chindo; Miele, Lucio; Artavanis‐Tsakonas, Spyros

doi:10.1038/emboj.2012.129

Cited by 74 publications

(86 citation statements)

References 80 publications

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“…However, immune stimulation reduces its phosphorylation levels and alters its target genes to those encoding immune effectors, which results in decreased anabolism and increased immunity 136 . Mef2 has also been linked to the regulation of Eiger, which is the D. melanogaster homologue of TNF 141 . TNF signalling is involved in cell death pathways and immunity in a range of organisms from flies to humans, which suggests another link between metabolism and innate responses.…”

Section: Systemic Control Of the Immune Systemmentioning

confidence: 99%

Immunity in Drosophila melanogaster — from microbial recognition to whole-organism physiology

2014

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Since the discovery of antimicrobial peptide responses 40 years ago, the fruit fly Drosophila melanogaster has proven to be a powerful model for the study of innate immunity. Early work focused on innate immune mechanisms of microbial recognition and subsequent nuclear factor‑κB signal transduction. More recently, D. melanogaster has been used to understand how the immune response is regulated and coordinated at the level of the whole organism. For example, researchers have used this model in studies investigating interactions between the microbiota and the immune system at barrier epithelial surfaces that ensure proper nutritional and immune homeostasis both locally and systemically. In addition, studies in D. melanogaster have been pivotal in uncovering how the immune response is regulated by both endocrine and metabolic signalling systems, and how the immune response modifies these systems as part of a homeostatic circuit. In this Review, we briefly summarize microbial recognition and antiviral immunity in D. melanogaster, and we highlight recent studies that have explored the effects of organism‑wide regulation of the immune response and, conversely, the effects of the immune response on organism physiology.

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Section: Systemic Control Of the Immune Systemmentioning

confidence: 99%

Immunity in Drosophila melanogaster — from microbial recognition to whole-organism physiology

2014

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“…Notch signaling has been shown to direct cells into proliferative or apoptotic states in a context-specific manner (Pallavi et al, 2012). Interestingly, Notch has both cellautonomous and non-cell-autonomous effects on mitotic activity, which it can either promote or suppress depending on the cellular context.…”

Section: Proliferation and Apoptosismentioning

confidence: 99%

Notch signaling at a glance

Hori

Sen

Artavanis‐Tsakonas

2013

Journal of Cell Science

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473

455

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Cell–cell interactions define a quintessential aspect of multicellular development. Metazoan morphogenesis depends on a handful of fundamental, conserved cellular interaction mechanisms, one of which is defined by the Notch signaling pathway. Signals transmitted through the Notch surface receptor have a unique developmental role: Notch signaling links the fate of one cell with that of a cellular neighbor through physical interactions between the Notch receptor and the membrane-bound ligands that are expressed in an apposing cell. The developmental outcome of Notch signals is strictly dependent on the cellular context and can influence differentiation, proliferation and apoptotic cell fates. The Notch pathway is conserved across species (Artavanis-Tsakonas et al., 1999; Bray, 2006; Kopan and Ilagan, 2009). In humans, Notch malfunction has been associated with a diverse range of diseases linked to changes in cell fate and cell proliferation including cancer (Louvi and Artavanis-Tsakonas, 2012). In this Cell Science at a Glance article and the accompanying poster we summarize the molecular biology of Notch signaling, its role in development and its relevance to disease.

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“…In estrogen receptor (ER)-positive tumors, repression of putative MEF2-target genes correlates with aggressiveness, and high class-IIa HDAC expression is associated with reduced survival (Clocchiatti et al, 2013b). By contrast, in recurrent ER-positive mammary cancers, expression of MEF2s correlates with NOTCH1 protein levels (Pallavi et al, 2012). Although some reports point to a contribution of MEF2-dependent transcription to mammary gland neoplastic pathogenesis, data on the role of the MEF2-HDAC axis during normal gland development and homeostasis are lacking, and only little information is available on the role of the axis in epithelial cells (Ishikawa et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

The MEF2–HDAC axis controls proliferation of mammary epithelial cells and acini formation in vitro

Clocchiatti

Giorgio

Viviani

et al. 2015

Journal of Cell Science

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The myocyte enhancer factor 2 and histone deacetylase (MEF2-HDAC) axis is a master regulator of different developmental programs and adaptive responses in adults. In this paper, we have investigated the contribution of the axis to the regulation of epithelial morphogenesis, using 3D organotypic cultures of MCF10A cells as a model. We have demonstrated that MEF2 transcriptional activity is upregulated during acini formation, which coincides with exit from the proliferative phase. Upregulation of the transcription of MEF2 proteins is coupled to downregulation of HDAC7, which occurs independently from changes in mRNA levels, and proteasome-or autophagymediated degradation. During acini formation, the MEF2-HDAC axis contributes to the promotion of cell cycle exit, through the engagement of the CDK inhibitor CDKN1A. Only in proliferating cells can HDAC7 bind to the first intron of the CDKN1A gene, a region characterized by epigenetic markers of active promoters and enhancers. In cells transformed by the oncogene HER2 (ERBB2), acini morphogenesis is altered, MEF2 transcription is repressed and HDAC7 is continuously expressed. Importantly, reactivation of MEF2 transcriptional activity in these cells, through the use of a HER2 inhibitor or by enhancing MEF2 function, corrected the proliferative defect and re-established normal acini morphogenesis.

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Notch and Mef2 synergize to promote proliferation and metastasis through JNK signal activation inDrosophila

Cited by 74 publications

References 80 publications

Immunity in Drosophila melanogaster — from microbial recognition to whole-organism physiology

Immunity in Drosophila melanogaster — from microbial recognition to whole-organism physiology

Notch signaling at a glance

The MEF2–HDAC axis controls proliferation of mammary epithelial cells and acini formation in vitro

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