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Sandra Röhm et al.
European journal of medicinal chemistry, 208, 112721-112721 (2020-10-10)
The p38 MAPK cascade is a key signaling pathway linked to a multitude of physiological functions and of central importance in inflammatory and autoimmune diseases. Although studied extensively, little is known about how conformation-specific inhibitors alter signaling outcomes. Here, we
Kendall J Lough et al.
eLife, 8 (2019-12-14)
During organogenesis, precise control of spindle orientation balances proliferation and differentiation. In the developing murine epidermis, planar and perpendicular divisions yield symmetric and asymmetric fate outcomes, respectively. Classically, division axis specification involves centrosome migration and spindle rotation, events occurring early
Christos Karathanasis et al.
Science signaling, 13(614) (2020-01-16)
Ligand-induced tumor necrosis factor receptor 1 (TNFR1) activation controls nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling, cell proliferation, programmed cell death, and survival and is crucially involved in inflammation, autoimmune disorders, and cancer progression. Despite the relevance of
Rene Geissler et al.
Genes & development, 30(9), 1070-1085 (2016-05-07)
3'-untranslated regions (UTRs) specify post-transcriptional fates of mammalian messenger RNAs (mRNAs), yet knowledge of the underlying sequences and mechanisms is largely incomplete. Here, we identify two related novel 3' UTR motifs in mammals that specify transcript degradation. These motifs are
Anne-Marie Pauwels et al.
Molecular & cellular proteomics : MCP, 18(5), 909-922 (2019-02-28)
Dendritic cells (DCs) are professional phagocytes that use innate sensing and phagocytosis to internalize and degrade self as well as foreign material, such as pathogenic bacteria, within phagosomes. These intracellular compartments are equipped to generate antigenic peptides that serve as
Shiqiong Hu et al.
Molecular biology of the cell, 30(16), 2025-2036 (2019-06-20)
Contractile arrays of actin and myosin II filaments drive many essential processes in nonmuscle cells, including migration and adhesion. Sequential organization of actin and myosin along one dimension is followed by expansion into a two-dimensional network of parallel actomyosin fibers
Ray Chang et al.
Acta biomaterialia, 111, 221-231 (2020-05-23)
Gene transfection is important in biotechnology and is used to modify cells intrinsically. It can be conducted in cell suspension or after cell adhesion, where the efficiency is dependent on many factors such as the type of nanocarrier used and
Fadila Telarevic Cero et al.
American journal of physiology. Lung cellular and molecular physiology, 309(4), L378-L387 (2015-06-14)
Pulmonary hypertension is a serious condition that can lead to premature death. The mechanisms involved are incompletely understood although a role for the immune system has been suggested. Inflammasomes are part of the innate immune system and consist of the
Kyrie Pappas et al.
Communications biology, 4(1), 312-312 (2021-03-23)
Downregulation of the PTEN tumor suppressor transcript is frequent in breast cancer and associates with poor prognosis and triple-negative breast cancer (TNBC) when comparing breast cancers to one another. Here we show that in almost all cases, when comparing breast
Selma Esseghir et al.
Cancer research, 67(24), 11732-11741 (2007-12-20)
By screening a tissue microarray of invasive breast tumors, we have shown that the receptor tyrosine kinase RET (REarranged during Transfection) and its coreceptor GFR alpha 1 (GDNF receptor family alpha-1) are overexpressed in a subset of estrogen receptor-positive tumors.
Pascal Laforêt et al.
Acta neuropathologica communications, 7(1), 167-167 (2019-10-30)
Glycogen storage disorder type III (GSDIII), or debranching enzyme (GDE) deficiency, is a rare metabolic disorder characterized by variable liver, cardiac, and skeletal muscle involvement. GSDIII manifests with liver symptoms in infancy and muscle involvement during early adulthood. Muscle biopsy
Masako Hozoji et al.
The Journal of biological chemistry, 283(44), 30057-30063 (2008-09-11)
Cholesterol is an essential component of eukaryotic cells; at the same time, however, hyperaccumulation of cholesterol is harmful. Therefore, the ABCA1 gene, the product of which mediates secretion of cholesterol, is highly regulated at both the transcriptional and post-transcriptional levels.
Raquel Buj et al.
Aging, 13(3), 3290-3312 (2021-02-08)
Oncogene-induced senescence (OIS) is characterized by increased expression of the cell cycle inhibitor p16, leading to a hallmark cell cycle arrest. Suppression of p16 in this context drives proliferation, senescence bypass, and contributes to tumorigenesis. OIS cells are also characterized
Se-Yeon Park et al.
Cell death & disease, 11(9), 744-744 (2020-09-13)
Mixed lineage kinase domain-like (MLKL) is an essential molecule of necroptosis, a cell death process that is initiated by direct disruption of the plasma membrane. During necroptosis, MLKL is phosphorylated by receptor interacting protein kinase-3 (RIPK3 or RIP3), and then
Christian Grommes et al.
Cancer discovery, 7(9), 1018-1029 (2017-06-18)
Bruton tyrosine kinase (BTK) links the B-cell antigen receptor (BCR) and Toll-like receptors with NF-κB. The role of BTK in primary central nervous system (CNS) lymphoma (PCNSL) is unknown. We performed a phase I clinical trial with ibrutinib, the first-in-class
Amanda R Wasylishen et al.
Molecular cancer research : MCR, 16(10), 1523-1529 (2018-06-16)
Mutations in the death domain-associated protein (DAXX) have been recently identified in a substantial proportion of human pancreatic neuroendocrine tumors (PanNETs). Remarkably, however, little is known about the physiologic role(s) of DAXX despite in vitro studies suggesting potential functions. Most
Amritha Nair et al.
Nature medicine, 24(4), 505-511 (2018-03-27)
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer diagnosed in more than 200,000 women each year and is recalcitrant to targeted therapies. Although TNBCs harbor multiple hyperactive receptor tyrosine kinases (RTKs), RTK inhibitors have been largely ineffective
Ebsy Jaimon et al.
The Journal of biological chemistry, 297(6), 101422-101422 (2021-11-20)
ARL5B, an ARF-like small GTPase localized to the trans-Golgi, is known for regulating endosome-Golgi trafficking and promoting the migration and invasion of breast cancer cells. Although a few interacting partners have been identified, the mechanism of the shuttling of ARL5B
Midori Mukai et al.
BMC cell biology, 18(1), 28-28 (2017-08-31)
Eph signaling is known to induce contrasting cell behaviors such as promoting and inhibiting cell adhesion/spreading by altering F-actin organization and influencing integrin activities. We have previously demonstrated that EphA2 stimulation by ephrin-A1 promotes cell adhesion through interaction with integrins
Yingjie Xu et al.
The Journal of experimental medicine, 207(11), 2421-2437 (2010-10-13)
The actin cross-linking protein filamin A (FLNa) functions as a scaffolding protein and couples cell cytoskeleton to extracellular matrix and integrin receptor signaling. In this study, we report that FLNa suppresses invasion of breast cancer cells and regulates focal adhesion
Michael Hamm et al.
Nature communications, 12(1), 3707-3707 (2021-06-19)
While the major drivers of melanoma initiation, including activation of NRAS/BRAF and loss of PTEN or CDKN2A, have been identified, the role of key transcription factors that impose altered transcriptional states in response to deregulated signaling is not well understood.
Shujing Liu et al.
Nature communications, 9(1), 5426-5426 (2018-12-24)
Prolyl hydroxylase domain protein 2 (PHD2) is a well-known master oxygen sensor. However, the role of PHD2 in tumor initiation remains controversial. We find that during the transition of human nevi to melanoma, the expression of PHD2 protein is significantly decreased
Tuo Wei et al.
Nature communications, 11(1), 3232-3232 (2020-06-28)
CRISPR-Cas9 has emerged as a powerful technology that relies on Cas9/sgRNA ribonucleoprotein complexes (RNPs) to target and edit DNA. However, many therapeutic targets cannot currently be accessed due to the lack of carriers that can deliver RNPs systemically. Here, we
Christoph Schmutz et al.
Molecular & cellular proteomics : MCP, 12(10), 2952-2968 (2013-07-06)
The enteroinvasive bacterium Shigella flexneri invades the intestinal epithelium of humans. During infection, several injected effector proteins promote bacterial internalization, and interfere with multiple host cell responses. To obtain a systems-level overview of host signaling during infection, we analyzed the
Majd M Ariss et al.
Journal of cell science, 133(19) (2020-09-04)
The receptor tyrosine kinase (RTK) pathway plays an essential role in development and disease by controlling cell proliferation and differentiation. Here, we profile the Drosophila larval brain by single-cell RNA-sequencing and identify Amalgam (Ama), which encodes a cell adhesion protein
Tomohiro Chiba et al.
PloS one, 9(12), e116162-e116162 (2015-01-01)
Hypercholesterolemia is one of the key risk factors for coronary heart disease, a major cause of death in developed countries. Suppression of NPC1L1-mediated dietary and biliary cholesterol absorption is predicted to be one of the most effective ways to reduce
Jaimee E Hoefert et al.
The Journal of cell biology, 217(6), 2185-2204 (2018-04-01)
The microRNA (miRNA)-200 (miR-200) family is highly expressed in epithelial cells and frequently lost in metastatic cancer. Despite intensive studies into their roles in cancer, their targets and functions in normal epithelial tissues remain unclear. Importantly, it remains unclear how
Masashi Mizuno et al.
Physiological reports, 6(12), e13741-e13741 (2018-06-23)
To explore mechanisms by which SGLT2 inhibitors protect diabetic hearts from heart failure, we examined the effect of empagliflozin (Empa) on the ultrastructure of cardiomyocytes in the noninfarcted region of the diabetic heart after myocardial infarction (MI). OLETF, a rat
Daniel V Iwamoto et al.
Nature structural & molecular biology, 25(10), 918-927 (2018-09-19)
Actin-cross-linking proteins assemble actin filaments into higher-order structures essential for orchestrating cell shape, adhesion, and motility. Missense mutations in the tandem calponin homology domains of their actin-binding domains (ABDs) underlie numerous genetic diseases, but a molecular understanding of these pathologies
Cathrine K Fog et al.
EBioMedicine, 38, 142-153 (2018-12-01)
Gaucher Disease is caused by mutations of the GBA gene which encodes the lysosomal enzyme acid beta-glucosidase (GCase). GBA mutations commonly affect GCase function by perturbing its protein homeostasis rather than its catalytic activity. Heat shock proteins are well known
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