A5074852816- RNA Research and Splicing
- Metabolism, Diabetes, and Cancer
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Pancreatic function and diabetes
- Protein Kinase Regulation and GTPase Signaling
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- RNA regulation and disease
- Diabetes Treatment and Management
- Diabetes and associated disorders
- Cell Adhesion Molecules Research
- Cancer-related gene regulation
- Diabetes Management and Research
- Glycosylation and Glycoproteins Research
- PI3K/AKT/mTOR signaling in cancer
- Ubiquitin and proteasome pathways
- Cellular Mechanics and Interactions
- Signaling Pathways in Disease
- Muscle Physiology and Disorders
- RNA Interference and Gene Delivery
- Receptor Mechanisms and Signaling
- Cancer, Hypoxia, and Metabolism
- 14-3-3 protein interactions
- Monoclonal and Polyclonal Antibodies Research
Ospedale Policlinico San Martino
2013-2023
University of Genoa
1985-2015
Istituti di Ricovero e Cura a Carattere Scientifico
2012-2014
Alleanza Contro il Cancro
2003-2014
The Francis Crick Institute
2012
University of California, San Diego
2001-2010
Unidades Centrales Científico-Técnicas
2010
Consejo Superior de Investigaciones Científicas
2010
Howard Hughes Medical Institute
2010
Istituto Nazionale per le Ricerche Cardiovascolari
2004
Transfected Chinese hamster ovary cell lines were developed that expressed equivalent numbers of either normal human receptor or had alanine substituted for Lys-1018 in the ATP-binding domain beta subunit. The mutated was processed into subunits and bound insulin but lacked protein tyrosine kinase activity. Five effects assayed: deoxyglucose uptake, S6 activity, endogenous protein-tyrosine phosphorylation, glycogen synthesis, thymidine uptake. In each case, cells bearing receptors...
Regulated mRNA turnover is a highly important process, but its mechanism poorly understood. Using interleukin-2 (IL-2) as model, we described role for the JNK-signaling pathway in stabilization of IL-2 during T-cell activation, acting via JNK response element (JRE) 5′ untranslated region (UTR). We have now identified two major RNA-binding proteins, nucleolin and YB-1, that specifically bind to JRE. Binding both proteins required induced by activation signals JNK-induced cell-free system...
The importance of post-transcriptional mechanisms for the regulation homoeostasis immune system and response to challenge by microorganisms is becoming increasingly appreciated. We investigated contribution microRNAs (miRNAs) macrophage activation induced lipopolysaccharide (LPS). first observed that Dicer knockout in bone marrow-derived macrophages (BMDMs) increases LPS-induced expression some inflammation mediators. miRNA microarray analysis BMDMs revealed LPS significantly induces a...
We have previously demonstrated that the human insulin receptor, mutated in ATP-binding domain of beta-subunit, is kinase-defective and fails to mediate multiple post-receptor actions stably transfected Chinese hamster ovary cells (Chou, C.-K., Dull, T. J., Russell, D. S., Gherzi, R., Lebwohl, D., Ullrich, A., Rosen, O. M. (1987) J. Biol. Chem. 262, 1842-1847). This study addresses role protein-tyrosine kinase activity insulin-mediated receptor down-regulation. Although mutant proreceptor...
In eukaryotes, RNA-binding proteins that contain multiple K homology (KH) domains play a key role in coordinating the different steps of RNA synthesis, metabolism and localization. Understanding how KH modules participate recognition targets is necessary to dissect way these operate. We have designed mutant with impaired capability for general use exploring individual combinatorial functional targets. A double mutation hallmark GxxG loop (GxxG-to-GDDG) impairs nucleic acid binding without...
Significance Long noncoding RNAs (lncRNAs) provide new layers of complexity to gene expression control. We report on the functional consequences interaction between ssRNA-binding protein K homology-type splicing regulatory (KSRP) with H19 lncRNA (H19) in multipotent C2C12 cells able differentiate culture toward myotubes response activation cell signaling pathways, including AKT. KSRP and interact exclusively undifferentiated cells, this favors KSRP’s ability promyogenic transcript myogenin...
Beta-catenin plays an essential role in several biological events including cell fate determination, proliferation, and transformation. Here we report that beta-catenin is encoded by a labile transcript whose half-life prolonged Wnt phosphatidylinositol 3-kinase-AKT signaling. AKT phosphorylates the mRNA decay-promoting factor KSRP at unique serine residue, induces its association with multifunctional protein 14-3-3, prevents interaction exoribonucleolytic complex exosome. This impairs...
Inherently unstable mRNAs contain AU-rich elements (AREs) in their 3' untranslated regions that act as mRNA stability determinants by interacting with ARE-binding proteins (ARE-BPs). We have destabilized two fusing sequence-specific RNA-binding to KSRP, a decay-promoting ARE-BP, tethering assay. These results support model KSRP recruits decay machinery/factors elicit decay. The ability of tethered depends on functions known enzymes. By targeting the Rev response element human...
The mechanism (both at the whole body and cellular level) by which metformin improves insulin sensitivity has yet to be defined. In present study, we examined in vivo insulin-mediated whole-body glucose disposal, glycogen synthesis, hepatic production, secretion, as well vitro muscle receptor tyrosine kinase activity eight control, neonatal streptozotocin diabetic rats, rats before after treatment with metformin. Ten weeks birth had higher fasting (132 + 5 v 101 2 mg/dL) postmeal (231 10 133...
Inherently unstable mRNAs contain AU-rich elements (AREs) in the 3′ untranslated regions. Expression of ARE-containing type I interferon transcripts is robustly induced upon viral infection and rapidly shut off thereafter. Their transient accumulation partly mediated through posttranscriptional regulation. Here we show that mouse embryonic fibroblasts derived from knockout mice deficient KH-type splicing regulatory protein (KSRP), an RNA-binding required for ARE-mediated mRNA decay, produce...
Abstract Long noncoding RNAs (lncRNAs) are emerging as regulators of fundamental biological processes. Here we report on the characterization an intergenic lncRNA expressed in epithelial tissues which termed EPR (Epithelial cell Program Regulator). is rapidly downregulated by TGF-β and its sustained expression largely reshapes transcriptome, favors acquisition traits, reduces proliferation cultured mammary gland cells well animal model orthotopic transplantation. generates a small peptide...
Epithelial-to-mesenchymal transition (EMT) confers several traits to cancer cells that are required for malignant progression. Here, we report miR-27b-3p-mediated silencing of the single-strand RNA binding protein KHSRP is transforming growth factor β (TGF-β)-induced EMT in mammary gland cells. Sustained expression limits TGF-β-dependent induction factors and cell migration, whereas its knockdown untreated mimics TGF-β-induced EMT. Genome-wide sequencing analyses revealed controls (1) levels...
White adipose tissue (WAT) releases fatty acids from stored triacylglycerol for an energy source. Here, we report that targeted deletion of KH-type splicing regulatory protein (KSRP), RNA-binding regulates gene expression at multiple levels, enhances lipolysis in epididymal WAT (eWAT) because the upregulation genes promoting lipolytic activity. Expression microRNA 145 (miR-145) is decreased impaired primary miR-145 processing Ksrp(-/-) eWAT. We show directly targets and represses Foxo1...