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p53 protects us from cancer by transcriptionally regulating tumor suppressive programs designed to either prevent the development or clonal expansion of malignant cells. How p53 selects target genes in the genome in a context- and tissue-specific manner remains largely obscure. There is growing evidence that the ability of p53 to bind DNA in a cooperative(More)
Comparative analysis is a topic of utmost importance in structural bioinformatics. Recently, a structural counterpart to sequence alignment, called multiple graph alignment, was introduced as a tool for the comparison of protein structures in general and protein binding sites in particular. Using approximate graph matching techniques, this method enables(More)
The multifunctional β-galactoside-binding protein galectin-3 is found in many distinct subcellular compartments including the cell nucleus. Expression and distribution of galectin-3 between the cell nucleus and the cytosol changes during cell differentiation and cancer development. Nuclear functions of galectin-3 and how they contribute to tumorigenesis are(More)
Senescence, perceived as a cancer barrier, is paradoxically associated with inflammation, which promotes tumorigenesis. Here, we characterize a distinct low-grade inflammatory process in stressed epithelium that is related to para-inflammation; this process either represses or promotes tumorigenesis, depending on p53 activity. Csnk1a1 (CKIα) downregulation(More)
The concept of multiple graph alignment (MGA) has recently been introduced as a novel method for the structural analysis of biomolecules. Using approximate graph matching techniques, this method enables the robust identification of approximately conserved patterns in biologically related structures. In particular, MGA enables the characterization of(More)
Inactivation of the p53 tumor suppressor by Mdm2 is one of the most frequent events in cancer, so compounds targeting the p53-Mdm2 interaction are promising for cancer therapy. Mechanisms conferring resistance to p53-reactivating compounds are largely unknown. Here we show using CRISPR-Cas9-based target validation in lung and colorectal cancer that the(More)
Predicting the sub-cellular localization of proteins is an important task in bioinformatics, for which many standard prediction tools are available. While these tools are powerful in general and capable of predicting protein localization for the most common compartments, their performance strongly depends on the organism of interest. More importantly, there(More)
In adaptation to oncogenic signals, pancreatic ductal adenocarcinoma (PDAC) cells undergo epithelial-mesenchymal transition (EMT), a process combining tumor cell dedifferentiation with acquisition of stemness features. However, the mechanisms linking oncogene-induced signaling pathways with EMT and stemness remain largely elusive. Here, we uncover the(More)
Protein binding sites are often represented by means of graphs capturing their most important geometrical and physicochemical properties. Searching for structural similarities and identifying functional relationships between them can thus be reduced to matching their corresponding graph descriptors. In this paper, we propose a method for the structural(More)
Graphs are often used to describe and analyze the geometry and physic-ochemical composition of biomolecular structures, such as chemical compounds and protein active sites. Ak ey problem in graph-based structure analysis is to define a measure of similarity that enables am eaningful comparison of such structures. In this regard, so-called kernel functions(More)