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Niehrs C.,German Cancer Research Center | Niehrs C.,Institute of Molecular Biology | Acebron S.P.,German Cancer Research Center
EMBO Journal | Year: 2012

Canonical Wnt signalling plays an important role in development, tissue homeostasis, and cancer. At the cellular level, canonical Wnt signalling acts by regulating cell fate, cell growth, and cell proliferation. With regard to proliferation, there is increasing evidence for a complex interaction between canonical Wnt signalling and the cell cycle. Mitogenic Wnt signalling regulates cell proliferation by promoting G1 phase. In mitosis, components of the Wnt signalling cascade function directly in spindle formation. Moreover, Wnt signalling is strongly activated in mitosis, suggesting that 'mitotic Wnt signalling' plays an important role to orchestrate a cell division program. Here, we review the complex interplay between Wnt signalling and the cell cycle. © 2012 European Molecular Biology Organization. Source

Niehrs C.,German Cancer Research Center | Niehrs C.,Institute of Molecular Biology
Nature Reviews Molecular Cell Biology | Year: 2012

30 years after the identification of WNTs, their signal transduction has become increasingly complex, with the discovery of more than 15 receptors and co-receptors in seven protein families. The recent discovery of three receptor classes for the R-spondin family of WNT agonists further adds to this complexity. What emerges is an intricate network of receptors that form higher-order ligand-receptor complexes routing downstream signalling. These are regulated both extracellularly by agonists such as R-spondin and intracellularly by post-translational modifications such as phosphorylation, proteolytic processing and endocytosis. © 2012 Macmillan Publishers Limited. All rights reserved. Source

Ulrich H.D.,Institute of Molecular Biology
Nature Structural and Molecular Biology | Year: 2014

Many aspects of nucleic acid metabolism, such as DNA replication, repair and transcription, are regulated by the post-translational modifiers ubiquitin and SUMO. Not surprisingly, DNA itself plays an integral part in determining the modification of most chromatin-associated targets. Conversely, ubiquitination or SUMOylation of a protein can impinge on its DNA-binding properties. This review describes mechanistic principles governing the mutual interactions between DNA and ubiquitin or SUMO. © 2014 Nature America, Inc. Source

Freuling C.M.,Institute of Molecular Biology
Philosophical transactions of the Royal Society of London. Series B, Biological sciences | Year: 2013

Despite perceived challenges to controlling an infectious disease in wildlife, oral rabies vaccination (ORV) of foxes has proved a remarkably successful tool and a prime example of a sophisticated strategy to eliminate disease from wildlife reservoirs. During the past three decades, the implementation of ORV programmes in 24 countries has led to the elimination of fox-mediated rabies from vast areas of Western and Central Europe. In this study, we evaluated the efficiency of 22 European ORV programmes between 1978 and 2010. During this period an area of almost 1.9 million km² was targeted at least once with vaccine baits, with control taking between 5 and 26 years depending upon the country. We examined factors influencing effort required both to control and eliminate fox rabies as well as cost-related issues of these programmes. The proportion of land area ever affected by rabies and an index capturing the size and overlap of successive ORV campaigns were identified as factors having statistically significant effects on the number of campaigns required to both control and eliminate rabies. Repeat comprehensive campaigns that are wholly overlapping much more rapidly eliminate infection and are less costly in the long term. Disproportionally greater effort is required in the final phase of an ORV programme, with a median of 11 additional campaigns required to eliminate disease once incidence has been reduced by 90 per cent. If successive ORV campaigns span the entire affected area, rabies will be eliminated more rapidly than if campaigns are implemented in a less comprehensive manner, therefore reducing ORV expenditure in the longer term. These findings should help improve the planning and implementation of ORV programmes, and facilitate future decision-making by veterinary authorities and policy-makers. Source

Schafer A.,Institute of Molecular Biology
Advances in Experimental Medicine and Biology | Year: 2013

The three growth arrest and DNA damage 45 (Gadd45) family genes encode for stress-response proteins that are rapidly induced upon cellular stress or differentiation cues. They are well-characterized regulators of cell cycle, senescence, survival, and apoptosis. More recently, it has become clear that Gadd45 proteins promote active DNA demethylation thereby mediating gene activation. This epigenetic function of Gadd45 is important for differentiation and transcriptional regulation during development. Mechanistically, Gadd45 acts as an adapter for DNA repair factors at gene-specific loci to promote removal of 5-methylcytosine from DNA. Hence, Gadd45 is a nexus between DNA repair and epigenetic gene regulation. © Springer Science+Business Media New York 2013. Source

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