TY - JOUR A1 - Philipp, Marius A1 - Dietz, Andreas A1 - Buchelt, Sebastian A1 - Kuenzer, Claudia T1 - Trends in satellite earth observation for permafrost related analyses — A review JF - Remote Sensing N2 - Climate change and associated Arctic amplification cause a degradation of permafrost which in turn has major implications for the environment. The potential turnover of frozen ground from a carbon sink to a carbon source, eroding coastlines, landslides, amplified surface deformation and endangerment of human infrastructure are some of the consequences connected with thawing permafrost. Satellite remote sensing is hereby a powerful tool to identify and monitor these features and processes on a spatially explicit, cheap, operational, long-term basis and up to circum-Arctic scale. By filtering after a selection of relevant keywords, a total of 325 articles from 30 international journals published during the last two decades were analyzed based on study location, spatio- temporal resolution of applied remote sensing data, platform, sensor combination and studied environmental focus for a comprehensive overview of past achievements, current efforts, together with future challenges and opportunities. The temporal development of publication frequency, utilized platforms/sensors and the addressed environmental topic is thereby highlighted. The total number of publications more than doubled since 2015. Distinct geographical study hot spots were revealed, while at the same time large portions of the continuous permafrost zone are still only sparsely covered by satellite remote sensing investigations. Moreover, studies related to Arctic greenhouse gas emissions in the context of permafrost degradation appear heavily underrepresented. New tools (e.g., Google Earth Engine (GEE)), methodologies (e.g., deep learning or data fusion etc.)and satellite data (e.g., the Methane Remote Sensing LiDAR Mission (Merlin) and the Sentinel-fleet)will thereby enable future studies to further investigate the distribution of permafrost, its thermal state and its implications on the environment such as thermokarst features and greenhouse gas emission rates on increasingly larger spatial and temporal scales. KW - satellite remote sensing KW - permafrost KW - degradation KW - thaw KW - thermokarst Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234198 VL - 13 IS - 6 ER - TY - JOUR A1 - Murakawa, Yasuhiro A1 - Hinz, Michael A1 - Mothes, Janina A1 - Schuetz, Anja A1 - Uhl, Michael A1 - Wyler, Emanuel A1 - Yasuda, Tomoharu A1 - Mastrobuoni, Guido A1 - Friedel, Caroline C. A1 - Dölken, Lars A1 - Kempa, Stefan A1 - Schmidt-Supprian, Marc A1 - Blüthgen, Nils A1 - Backofen, Rolf A1 - Heinemann, Udo A1 - Wolf, Jana A1 - Scheidereit, Claus A1 - Landthaler, Markus T1 - RC3H1 post-transcriptionally regulates A20 mRNA and modulates the activity of the IKK/NF-\(\kappa\)B pathway JF - Nature Communications N2 - The RNA-binding protein RC3H1 (also known as ROQUIN) promotes TNF\(\alpha\) mRNA decay via a 3'UTR constitutive decay element (CDE). Here we applied PAR-CLIP to human RC3H1 to identify ~3,800 mRNA targets with >16,000 binding sites. A large number of sites are distinct from the consensus CDE and revealed a structure-sequence motif with U-rich sequences embedded in hairpins. RC3H1 binds preferentially short-lived and DNA damage-induced mRNAs, indicating a role of this RNA-binding protein in the post-transcriptional regulation of the DNA damage response. Intriguingly, RC3H1 affects expression of the NF-\(\kappa\)B pathway regulators such as I\(\kappa\)B\(\alpha\) and A20. RC3H1 uses ROQ and Zn-finger domains to contact a binding site in the A20 3'UTR, demonstrating a not yet recognized mode of RC3H1 binding. Knockdown of RC3H1 resulted in increased A20 protein expression, thereby interfering with I\(\kappa\)B kinase and NF-\(\kappa\)B activities, demonstrating that RC3H1 can modulate the activity of the IKK/NF-\(\kappa\)B pathway. KW - large gene lists KW - decay KW - identification KW - stress KW - binding protein KW - RQQ domain KW - autoimmunity KW - complex KW - degradation KW - motifs Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151596 VL - 6 IS - 7367 ER - TY - JOUR A1 - Frank, Daniel O. A1 - Dengjel, Jörn A1 - Wilfling, Florian A1 - Kozjak-Pavlovic, Vera A1 - Häcker, Georg A1 - Weber, Arnim T1 - The Pro-Apoptotic BH3-Only Protein Bim Interacts with Components of the Translocase of the Outer Mitochondrial Membrane (TOM) JF - PLoS ONE N2 - The pro-apoptotic Bcl-2-family protein Bim belongs to the BH3-only proteins known as initiators of apoptosis. Recent data show that Bim is constitutively inserted in the outer mitochondrial membrane via a C-terminal transmembrane anchor from where it can activate the effector of cytochrome c-release, Bax. To identify regulators of Bim-activity, we conducted a search for proteins interacting with Bim at mitochondria. We found an interaction of Bim with Tom70, Tom20 and more weakly with Tom40, all components of the Translocase of the Outer Membrane (TOM). In vitro import assays performed on tryptically digested yeast mitochondria showed reduced Bim insertion into the outer mitochondrial membrane (OMM) indicating that protein receptors may be involved in the import process. However, RNAi against components of TOM (Tom40, Tom70, Tom22 or Tom20) by siRNA, individually or in combination, did not consistently change the amount of Bim on HeLa mitochondria, either at steady state or upon de novo-induction. In support of this, the individual or combined knockdowns of TOM receptors also failed to alter the susceptibility of HeLa cells to Bim-induced apoptosis. In isolated yeast mitochondria, lack of Tom70 or the TOM-components Tom20 or Tom22 alone did not affect the import of Bim into the outer mitochondrial membrane. In yeast, expression of Bim can sensitize the cells to Bax-dependent killing. This sensitization was unaffected by the absence of Tom70 or by an experimental reduction in Tom40. Although thus the physiological role of the Bim-TOM-interaction remains unclear, TOM complex components do not seem to be essential for Bim insertion into the OMM. Nevertheless, this association should be noted and considered when the regulation of Bim in other cells and situations is investigated. KW - bax KW - preproteins KW - phosphorylation KW - proteomics KW - degradation KW - cells KW - family KW - import KW - BH3 domains KW - Bcl-2 proteins Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143301 VL - 10 IS - 4 ER - TY - JOUR A1 - Ehrenschwender, M. A1 - Bittner, S. A1 - Seibold, K. A1 - Wajant, H. T1 - XIAP-targeting drugs re-sensitize PIK3CA-mutated colorectal cancer cells for death receptor-induced apoptosis JF - Cell Death & Disease N2 - Mutations in the oncogenic PIK3CA gene are found in 10-20% of colorectal cancers (CRCs) and are associated with poor prognosis. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and agonistic TRAIL death receptor antibodies emerged as promising anti-neoplastic therapeutics, but to date failed to prove their capability in the clinical setting as especially primary tumors exhibit high rates of TRAIL resistance. In our study, we investigated the molecular mechanisms underlying TRAIL resistance in CRC cells with a mutant PIK3CA (PIK3CA-mut) gene. We show that inhibition of the constitutively active phosphatidylinositol-3 kinase (PI3K)/Akt signaling pathway only partially overcame TRAIL resistance in PIK3CA-mut-protected HCT116 cells, although synergistic effects of TRAIL plus PI3K, Akt or cyclin-dependent kinase (CDK) inhibitors could be noted. In sharp contrast, TRAIL triggered full-blown cell death induction in HCT116 PIK3CA-mut cells treated with proteasome inhibitors such as bortezomib and MG132. At the molecular level, resistance of HCT116 PIK3CA-mut cells against TRAIL was reflected by impaired caspase-3 activation and we provide evidence for a crucial involvement of the E3-ligase X-linked inhibitor of apoptosis protein (XIAP) therein. Drugs interfering with the activity and/or the expression of XIAP, such as the second mitochondria-derived activator of caspase mimetic BV6 and mithramycin-A, completely restored TRAIL sensitivity in PIK3CA-mut-protected HCT116 cells independent of a functional mitochondrial cell death pathway. Importantly, proteasome inhibitors and XIAP-targeting agents also sensitized other CRC cell lines with mutated PIK3CA for TRAIL-induced cell death. Together, our data suggest that proteasome-or XIAP-targeting drugs offer a novel therapeutic approach to overcome TRAIL resistance in PIK3CA-mutated CRC. KW - trail-mediated apoptosis KW - ligand trail KW - CASPASE-3 KW - resistance KW - BH3-only proteins KW - inhibitor KW - MCL-1 KW - degradation KW - activation KW - carcinoma Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-114374 SN - 2041-4889 VL - 5 ER -