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Regulation of histone modification and chromatin structure by the p53–PADI4 pathway
PADI4 is an enzyme that converts arginine residues to citrulline. Here, Tanikawa and colleagues show that, in response to DNA damage, histone H4 and Lamin C are citrullinated in a p53 and PADI4-dependent manner andPadi4-dependent manner and Padi4 null mice are resistant to radiation-induced apoptosis in the thymus.
- Chizu Tanikawa
- , Martha Espinosa
- & Koichi Matsuda
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Article
| Open AccessActivation of TRPC6 channels is essential for lung ischaemia–reperfusion induced oedema in mice
The signalling cascade involved in lung ischaemia–reperfusion-induced oedema is poorly understood. Using knockout mice, Weissmannet al. propose a model in which reactive oxygen species production by endothelial NOX2 leads to phospholipase C-γ activation, DAG kinase inhibition and subsequent TRPC6 activation.
- Norbert Weissmann
- , Akylbek Sydykov
- & Alexander Dietrich
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Ectopic expression of the histone methyltransferase Ezh2 in haematopoietic stem cells causes myeloproliferative disease
The histone methyltransferase Ezh2 is thought to have a dual function both as a tumour suppressor and an oncogene. Using mouse models with Ezh2 gain-of-function, Herrera-Merchanet al. show that Ezh2 expression in HSCs severely compromises hematopoietic function, leading to myeloproliferative disease.
- A. Herrera-Merchan
- , L. Arranz
- & S. Gonzalez
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Article
| Open AccessActivin enhances skin tumourigenesis and malignant progression by inducing a pro-tumourigenic immune cell response
Activin is known to have a role in wound healing, but its role in skin cancer is unknown. Antsiferovaet al. show that activin is elevated in human skin tumours, and by modulating epidermal immune cells, exacerbates tumour progression in a mouse model of skin cancer.
- Maria Antsiferova
- , Marcel Huber
- & Sabine Werner
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Article
| Open AccessPAR2 absence completely rescues inflammation and ichthyosis caused by altered CAP1/Prss8 expression in mouse skin
The activity of serine proteases, including CAP1/Prss8, is altered in some human skin disorders; however, the downstream effectors of these proteins are relatively unknown. Here, using animal models, the authors show that protease-activated receptor-2 is a critical component of the CAP1/Prss8 signalling cascade.
- Simona Frateschi
- , Eric Camerer
- & Edith Hummler
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Article
| Open AccessStretching fibronectin fibres disrupts binding of bacterial adhesins by physically destroying an epitope
Bacteria express adhesive proteins on their surface that recognize fibronectin. Using a mechanical stretch assay and steered molecular dynamics, Chabriaet al. demonstrate that the binding of a bacterial adhesin to fibronectin is mechanoregulated, suggesting that bacteria can sense tissue fibre stretching.
- Mamta Chabria
- , Samuel Hertig
- & Viola Vogel