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Concept

Oncogene

Related publications (28)

Whole-genome doubling drives oncogenic loss of chromatin segregation

Elisa Oricchio, Natalya Katanayeva, Daniele Tavernari, Ruxandra-Andreea Lambuta, Juan Diaz Miyar

Whole-genome doubling (WGD) is a recurrent event in human cancers and it promotes chromosomal instability and acquisition of aneuploidies(1-8). However, the three-dimensional organization of chromatin in WGD cells and its contribution to oncogenic phenotyp ...

NATURE PORTFOLIO2023

Histone acetylation dynamics modulates chromatin conformation and allele-specific interactions at oncogenic loci

Elisa Oricchio, Daniele Tavernari, Natalya Katanayeva, Stephanie Jocelyne Sungalee, Ruxandra-Andreea Lambuta

In cancer cells, enhancer hijacking mediated by chromosomal alterations and/or increased deposition of acetylated histone H3 lysine 27 (H3K27ac) can support oncogene expression. However, how the chromatin conformation of enhancer-promoter interactions is a ...

2021

Btk SH2-kinase interface is critical for allosteric kinase activation and its targeting inhibits B-cell neoplasms

Matteo Dal Peraro, Oliver Hantschel, Florence Pojer, Sandrine Madeleine Suzanne Georgeon, Maria Josefina Marcaida Lopez, Allan Joaquim Lamontanara, Grégory La Sala, Tim Kükenshöner, Daniel Pereira Duarte

Bruton's tyrosine kinase (Btk) is critical for B-cell maturation and activation. Btk loss-of-function mutations cause human X-linked agammaglobulinemia (XLA). In contrast, Btk signaling sustains growth of several B-cell neoplasms which may be treated with ...

Nature Publishing Group2020

Characterization of the Renin-Angiotensin System in Aged Cavernosal Tissue and its Role in Penile Fibrosis

Nikolaos Stergiopoulos, Mikaël Nils Sturny, Maiia Bragina

Background: The renin-angiotensin system (RAS) plays an important role in erectile function. The RAS contains 2 major axes: one deleterious, composed of ACE-Ang II-AT1 receptor, and another protective, composed of ACE2-Ang-(1-7)-Mas receptor. While aging i ...

ELSEVIER SCI LTD2020

γ-Catenin-Dependent Signals Maintain BCR-ABL1+ B Cell Acute Lymphoblastic Leukemia

Oliver Hantschel, Jörg Hülsken, Anja Irmisch

The BCR-ABL1 fusion protein is the cause of chronic myeloid leukemia (CML) and of a significant fraction of adult-onset B cell acute lymphoblastic leukemia (B-ALL) cases. Using mouse models and patient-derived samples, we identified an essential role for γ ...

2019

CRISPR-Cas9-mediated saturated mutagenesis screen predicts clinical drug resistance with improved accuracy

Jeffrey David Jensen, Sebastian Matuszewski

Developing tools to accurately predict the clinical prevalence of drug-resistant mutations is a key step toward generating more effective therapeutics. Here we describe a high-throughput CRISPR-Cas9-based saturated mutagenesis approach to generate comprehe ...

National Academy of Sciences2017

Allosteric kinase inhibitors

Oliver Hantschel

Background. Inhibition of the kinase activity of the BCR-ABL1 oncoprotein by an allosteric mechanism of action facilitates alternative treatment options for chronic myeloid leukemia (CML) patients who cannot be adequately treated with conventional catalyti ...

Springer Nature2017

Differential signaling networks of Bcr-Abl p210 and p190 kinases in leukemia cells defined by functional proteomics

Romain Hamelin, Sandrine Madeleine Suzanne Georgeon, Oliver Hantschel, Sina Maren Reckel

The two major isoforms of the oncogenic Bcr-Abl tyrosine kinase, p210 and p190, are expressed upon the Philadelphia chromosome translocation. p210 is the hallmark of chronic myelogenous leukemia, whereas p190 occurs in the majority of B-cell acute lymphobl ...

Nature Publishing Group2017

Normal ABL1 is a tumor suppressor and therapeutic target in human and mouse leukemias expressing oncogenic ABL1 kinases

Oliver Hantschel

Leukemias expressing constitutively activated mutants of ABL1 tyrosine kinase (BCR-ABL1, TEL-ABL1, NUP214-ABL1) usually contain at least 1 normal ABL1 allele. Because oncogenic and normal ABL1 kinases may exert opposite effects on cell behavior, we examine ...

American Society of Hematology2016

Allosteric regulation and targeting of Abl SH2-kinase interface and other cytoplasmic tyrosine kinases

Allan Joaquim Lamontanara

Due to their central role in normal cellular physiology, the activity of protein kinases is tightly regulated and their aberrant activation can lead to cancer. Chronic myelogenous leukemia (CML) is a blood cancer characterized by unregulated growth of myel ...

EPFL2016

Role of RIP4 in lung adenocarcinoma differentiation

Jawahar Kopparam

Various studies have attributed NF-kB activation to promote KRAS mediated non-small cell lung cancer progression. In order to identify key genes regulating NF-kB activation and cell survival in lung adenocarcinoma, a synthetic lethal partner screen for KRA ...

EPFL2016

Single Molecule Localization and Discrimination of DNA–Protein Complexes by Controlled Translocation Through Nanocapillaries

Aleksandra Radenovic, Sebastian Maerkl, Sanjin Marion, Roman Bulushev, Sebastian James Davis, Ekaterina Emilova Petrova

Through the use of optical tweezers we performed controlled translocations of DNA-protein complexes through nanocapillaries. We used RNA polymerase (RNAP) with two binding sites on a 7.2 kbp DNA fragment and a dCas9 protein tailored to have five binding si ...

American Chemical Society (ACS)2016

Functional Perturbation of the Gab2 Multiprotein Complex by High-affinity SH2-binding Monobodies in Chronic Myelogenous Leukemia

Emel Basak Gencer Akçok

Chronic myeloid leukemia is characterized by a reciprocal chromosomal translocation between chromosome 9 and 22, resulting in the expression of the Bcr-Abl oncoprotein. Despite the great improvement in patient survival using tyrosine kinase inhibitors (TKI ...

EPFL2015

Crystal structure of an SH2-kinase construct of c-Abl and effect of the SH2 domain on kinase activity

Oliver Hantschel

Constitutive activation of the non-receptor tyrosine kinase c-Abl (cellular Abelson tyrosine protein kinase 1, Abl1) in the Bcr (breakpoint cluster region)-Abl1 fusion oncoprotein is the molecular cause of chronic myeloid leukaemia (CML). Recent studies ha ...

Portland Press2015

Malaria Parasite-Infected Erythrocytes Secrete PfCK1, the Plasmodium Homologue of the Pleiotropic Protein Kinase Casein Kinase 1

Romain Hamelin, Florence Armand, Marc Moniatte

Casein kinase 1 (CK1) is a pleiotropic protein kinase implicated in several fundamental processes of eukaryotic cell biology. Plasmodium falciparum encodes a single CK1 isoform, PfCK1, that is expressed at all stages of the parasite's life cycle. We have p ...

Public Library of Science2015

Targeting cytokine networks in KRAS-driven tumorigenesis

KRAS is one of the most commonly mutated oncogenes in human tumors, and is typically associated with aggressive disease. Despite intensive study and years of effort, KRAS has remained refractory to targeted inhibition. Given the challenge of inhibiting KRA ...

Expert Reviews2014

The SH2 domain of Abl kinases regulates kinase autophosphorylation by controlling activation loop accessibility

Oliver Hantschel, Sandrine Madeleine Suzanne Georgeon, Allan Joaquim Lamontanara

The activity of protein kinases is regulated by multiple molecular mechanisms, and their disruption is a common driver of oncogenesis. A central and almost universal control element of protein kinase activity is the activation loop that utilizes both confo ...

Nature Research2014

Calnexin Controls the STAT3-Mediated Transcriptional Response to EGF

Françoise Gisou van der Goot Grunberg

Calnexin is a well-characterized transnnembrane chaperone involved in the folding of newly synthesized glycoproteins in the lumen of the endoplasmic reticulum (ER). Here, we reveal a previously unrecognized function of calnexin in regulating the transcript ...

Elsevier2013

Dissection of the BCR-ABL signaling network using highly specific monobody inhibitors to the SHP2 SH2 domains

Oliver Hantschel, Sandrine Madeleine Suzanne Georgeon, Emel Basak Gencer Akçok

The dysregulated tyrosine kinase BCR-ABL causes chronic myelogenous leukemia in humans and forms a large multiprotein complex that includes the Src-homology 2 (SH2) domain-containing phosphatase 2 (SHP2). The expression of SHP2 is necessary for BCR-ABL-dep ...

National Academy of Sciences2013

RNA-Protein interactions at AU-rich elements

Ramona Pauchard-Batschulat

The expression of many proto-oncogenes, nuclear transcription factors and cytokines is regulated post-transcriptionally by specific interactions between distinct cis-elements within the mRNA and trans-acting factors that bind to these elements and thereby ...

EPFL2013