TY - JOUR A1 - Scharaw, Sandra A1 - Iskar, Murat A1 - Ori, Alessandro A1 - Boncompain, Gaelle A1 - Laketa, Vibor A1 - Poser, Ina A1 - Lundberg, Emma A1 - Perez, Franck A1 - Beck, Martin A1 - Bork, Peer A1 - Pepperkok, Rainer T1 - The endosomal transcriptional regulator RNF11 integrates degradation and transport of EGFR JF - Journal of Cell Biology N2 - Stimulation of cells with epidermal growth factor (EGF) induces internalization and partial degradation of the EGF receptor (EGFR) by the endo-lysosomal pathway. For continuous cell functioning, EGFR plasma membrane levels are maintained by transporting newly synthesized EGFRs to the cell surface. The regulation of this process is largely unknown. In this study, we find that EGF stimulation specifically increases the transport efficiency of newly synthesized EGFRs from the endoplasmic reticulum to the plasma membrane. This coincides with an up-regulation of the inner coat protein complex II (COP II) components SEC23B, SEC24B, and SEC24D, which we show to be specifically required for EGFR transport. Up-regulation of these COP II components requires the transcriptional regulator RNF11, which localizes to early endosomes and appears additionally in the cell nucleus upon continuous EGF stimulation. Collectively, our work identifies a new regulatory mechanism that integrates the degradation and transport of EGFR in order to maintain its physiological levels at the plasma membrane. KW - Epidermal growth-factor KW - finger protein 11 KW - receptor tyrosine kinases KW - early secretory pathway KW - breast-cancer KW - brefeldin-a KW - E3 ligase KW - trafficking KW - export KW - endoplasmic-reticulum Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186731 VL - 215 IS - 4 ER - TY - JOUR A1 - Vogtmann, Emily A1 - Hua, Xing A1 - Zeller, Georg A1 - Sunagawa, Shinichi A1 - Voigt, Anita Y. A1 - Hercog, Rajna A1 - Goedert, James J. A1 - Shi, Jianxin A1 - Bork, Peer A1 - Sinha, Rashmi T1 - Colorectal Cancer and the Human Gut Microbiome: Reproducibility with Whole-Genome Shotgun Sequencing JF - PLoS ONE N2 - Accumulating evidence indicates that the gut microbiota affects colorectal cancer development, but previous studies have varied in population, technical methods, and associations with cancer. Understanding these variations is needed for comparisons and for potential pooling across studies. Therefore, we performed whole-genome shotgun sequencing on fecal samples from 52 pre-treatment colorectal cancer cases and 52 matched controls from Washington, DC. We compared findings from a previously published 16S rRNA study to the metagenomics-derived taxonomy within the same population. In addition, metagenome-predicted genes, modules, and pathways in the Washington, DC cases and controls were compared to cases and controls recruited in France whose specimens were processed using the same platform. Associations between the presence of fecal Fusobacteria, Fusobacterium, and Porphyromonas with colorectal cancer detected by 16S rRNA were reproduced by metagenomics, whereas higher relative abundance of Clostridia in cancer cases based on 16S rRNA was merely borderline based on metagenomics. This demonstrated that within the same sample set, most, but not all taxonomic associations were seen with both methods. Considering significant cancer associations with the relative abundance of genes, modules, and pathways in a recently published French metagenomics dataset, statistically significant associations in the Washington, DC population were detected for four out of 10 genes, three out of nine modules, and seven out of 17 pathways. In total, colorectal cancer status in the Washington, DC study was associated with 39% of the metagenome-predicted genes, modules, and pathways identified in the French study. More within and between population comparisons are needed to identify sources of variation and disease associations that can be reproduced despite these variations. Future studies should have larger sample sizes or pool data across studies to have sufficient power to detect associations that are reproducible and significant after correction for multiple testing. KW - colorectal cancer KW - gut microbiota KW - whole-genome shotgun sequencing Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166904 VL - 11 IS - 5 ER - TY - JOUR A1 - Letunic, Ivica A1 - Bork, Peer T1 - Interactive tree of life (iTOL) v3: an online tool for the display and annotation of phylogenetic and other trees JF - Nucleic Acids Research N2 - Interactive Tree Of Life (http://itol.embl.de) is a web-based tool for the display, manipulation and annotation of phylogenetic trees. It is freely available and open to everyone. The current version was completely redesigned and rewritten, utilizing current web technologies for speedy and streamlined processing. Numerous new features were introduced and several new data types are now supported. Trees with up to 100,000 leaves can now be efficiently displayed. Full interactive control over precise positioning of various annotation features and an unlimited number of datasets allow the easy creation of complex tree visualizations. iTOL 3 is the first tool which supports direct visualization of the recently proposed phylogenetic placements format. Finally, iTOL's account system has been redesigned to simplify the management of trees in user-defined workspaces and projects, as it is heavily used and currently handles already more than 500,000 trees from more than 10,000 individual users. KW - Interactive Tree Of Life (iTOL) KW - phylogenetic trees KW - visualization KW - tool Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166181 VL - 44 IS - W1 ER -