Publications related to Ras GTPase

Mechanism of KRAS-driven T cell infiltration in colorectal cancer

Colorectal cancer is the second-leading cause of cancer death worldwide. Early-stage disease can be detected with preventative medical screening and is treatable with surgical resection. Sixty-percent of patients, however, are diagnosed with advanced-stage ...

EPFL2023

Modeling tumor size dynamics based on real-world electronic health records and image data in advanced melanoma patients receiving immunotherapy

Olivier Michielin, Federico Amato, Monia Guidi, Nadia Terranova, Daniel Abler, Alexandre Wicky

The development of immune checkpoint inhibitors (ICIs) has revolutionized cancer therapy but only a fraction of patients benefits from this therapy. Model-informed drug development can be used to assess prognostic and predictive clinical factors or biomark ...

2023

In vivo transcriptomic profiling using cell encapsulation identifies effector pathways of systemic aging

Patrick Descombes, Jérome Feige, Sylviane Métairon, Omid Mashinchian, Filippo De Franceschi, Nicolas Bouche, Christophe Boss

Sustained exposure to a young systemic environment rejuvenates aged organisms and promotes cellular function. However, due to the intrinsic complexity of tissues it remains challenging to pinpoint niche-independent effects of circulating factors on specifi ...

2022

Akt Is S-Palmitoylated: A New Layer of Regulation for Akt

Françoise Gisou van der Goot Grunberg, Laurence Gouzi Abrami

The protein kinase Akt/PKB participates in a great variety of processes, including translation, cell proliferation and survival, as well as malignant transformation and viral infection. In the last few years, novel Akt posttranslational modifications have ...

FRONTIERS MEDIA SA2021

Clofarabine Commandeers the RNR-alpha-ZRANB3 Nuclear Signaling Axis

Yimon Aye, Yi Zhao

Ribonucleotide reductase (RNR) is an essential enzyme in DNA biogenesis and a target of several chemotherapeutics. Here, we investigate how antileukemic drugs (e.g., clofarabine [CIF]) that target one of the two subunits of RNR, RNR-alpha, affect noncanoni ...

CELL PRESS2020

Dopaminergic neurodegeneration induced by Parkinson's disease-linked G2019S LRRK2 is dependent on kinase and GTPase activity

Elpida Tsika, Darren Moore, Xi Chen

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of late-onset, autosomal-dominant familial Parkinson's disease (PD). LRRK2 functions as both a kinase and GTPase, and PD-linked mutations are known to influence both enzymatic acti ...

National Academy of Sciences2020

Structural basis of Focal Adhesion Kinase activation on lipid membranes

Henning Paul-Julius Stahlberg, Frauke Gräter

Focal adhesion kinase (FAK) is a key component of the membrane proximal signaling layer in focal adhesion complexes, regulating important cellular processes, including cell migration, proliferation, and survival. In the cytosol, FAK adopts an autoinhibited ...

2020

Identification and characterisation of small-molecule inhibitors targeting STING

Simone Margret Haag

The recognition of pathogen-derived nucleic acids is a critical mechanism by which the innate immune system detects viral infection. Upon activation, nucleic acid sensors initiate the expression of type I interferons and other inflammatory mediators, subse ...

EPFL2019

RANKL Signaling Sustains Primary Tumor Growth in Genetically Engineered Mouse Models of Lung Adenocarcinoma

Nadine Fournier, Etienne Meylan, Julien Robert Rémi Faget, Caroline Anne-Lyse Contat

INTRODUCTION: NSCLC is the leading cause of cancer mortality. Recent retrospective clinical analyses suggest that blocking the receptor activator of NF-κB (RANK) signaling pathway inhibits the growth of NSCLC and might represent a new treatment strategy. M ...

2018

Novel systems biology approaches for design and analysis of palmitoylation networks reveal its regulatory effects on protein stability, activity and localization

Tiziano Dallavilla

Communication and environment sensing are fundamental for the regulation of the majority of the cellular functions. In cells there are dedicated networks that are responsible for signalling, which gives the ability to the cell of sensing the external and i ...

EPFL2017

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

AMP-activated protein kinase : strategies for activation and downstream target identification

Serge Thanh Son Ducommun

AMP-activated protein kinase (AMPK) is an evolutionally conserved key sensor of cellular energy status. Under conditions of cellular energy stress, AMPK is activated and will switch off anabolic processes that consume ATP, while activating catabolic proces ...

EPFL2016

MicroRNA-206 functions as a pleiotropic modulator of cell proliferation, invasion and lymphangiogenesis in pancreatic adenocarcinoma by targeting ANXA2 and KRAS genes

Yiming Cao

Recent advances in cancer biology have emerged important roles for microRNAs (miRNAs) in regulating tumor responses. However, their function in mediating intercellular communication within the tumor microenvironment is thus far poorly explored. Here, we fo ...

Nature Publishing Group2015

Targeting pathways downstream of KRAS in lung adenocarcinoma

Oncogenic KRAS activation is responsible for the most common genetic subtype of lung cancer. Although many of the major downstream signaling pathways that KRAS engages have been defined, these discoveries have yet to translate into effective targeted thera ...

Future Medicine Ltd2014

Mechanistic effects of protein palmitoylation and the cellular consequences thereof

Françoise Gisou van der Goot Grunberg, Sanja Blaskovic, Mathieu Blanc

S-palmitoylation involves the attachment of a 16-carbon long fatty acid chain to the cysteine residues of proteins. The process is enzymatic and dynamic with DHHC enzymes mediating palmitoylation and acyl-protein thioesterases reverting the reaction. Prote ...

Elsevier Ireland Ltd2014

A Parkinson's disease gene regulatory network identifies the signaling protein RGS2 as a modulator of LRRK2 activity and neuronal toxicity

Patrick Aebischer, Bernard Schneider, Julien Dusonchet, Liliane Glauser, Darren Moore, Klodjan Stafa

Mutations in LRRK2 are one of the primary genetic causes of Parkinson's disease (PD). LRRK2 contains a kinase and a GTPase domain, and familial PD mutations affect both enzymatic activities. However, the signaling mechanisms regulating LRRK2 and the pathog ...

Oxford University Press2014

Functional interaction of Parkinsons disease-associated LRRK2 with members of the dynamin GTPase superfamily

Liliane Glauser, Elpida Tsika, Klodjan Stafa, Darren Moore, Alessandra Musso, Amy Jones

Mutations in LRRK2 cause autosomal dominant Parkinsons disease (PD). LRRK2 encodes a multi-domain protein containing GTPase and kinase domains, and putative proteinprotein interaction domains. Familial PD mutations alter the GTPase and kinase activity of L ...

Oxford University Press2014

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 Bcl9-beta-catenin interface as a potential therapeutic target for colorectal cancer

Andreas Eduard Moor

Aberrantly active Wnt signaling is the hallmark driver of colorectal cancer (CRC). Bcl9/9l proteins are components of the main transcriptional activation complex of canonical Wnt signaling and interact with beta-catenin via a highly conserved homology doma ...

EPFL2014

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