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

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Mycobacterium tuberculosis possesses a thick and highly hydrophobic cell wall principally composed of a mycolyl-arabinogalactan-peptidoglycan complex, which is critical for survival and virulence. DprE1 is a well-characterized component of decaprenyl-phosp ...

Amer Soc Microbiology2015

NUP214-ABL1 mediated cell proliferation in T-cell acute lymphoblastic leukemia is dependent on the LCK kinase and various interacting proteins

Oliver Hantschel

The NUP214-ABL1 fusion protein is a constitutively active protein tyrosine kinase that is found in 6% of patients with T-cell acute lymphoblastic leukemia and that promotes proliferation and survival of T-lymphoblasts. Although NUP214-ABL1 is sensitive to ...

Pensiero Scientifico / Ferrata Storti Foundation2014

Assessing the role of Hes1 and identification of target genes in human and murine T-ALL

Silvia Wirth

The Notch signalling pathway is an ancient cell signalling mechanism that enables short-range communications between cells and controls a broad spectrum of cell fates and developmental processes. In the haematopoietic system Notch signalling has been linke ...

EPFL2014

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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 ...

2014

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, Liliane Glauser, Darren Moore, Klodjan Stafa, Julien Dusonchet

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, Darren Moore, Klodjan Stafa, Amy Jones, Alessandra Musso

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

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Increasing evidence suggests that the c-Abl protein tyrosine kinase could play a role in the pathogenesis of Parkinson's disease (PD) and other neurodegenerative disorders. c-Abl has been shown to regulate the degradation of two proteins implicated in the ...

Oxford University Press2014

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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

Mechanisms of resistance to BCR-ABL and other kinase inhibitors

Oliver Hantschel, Allan Joaquim Lamontanara, Emel Basak Gencer Akçok, Orest Kuzyk

In this article, we are reviewing the molecular mechanisms that lead to kinase inhibitor resistance. As the oncogenic BCR-ABL kinase is the target of the first approved small-molecule kinase inhibitor imatinib, we will first focus on the structural and mec ...

Elsevier Science Bv2013

Dynamic Impacts of the Inhibition of the Molecular Chaperone Hsp90 on the T-Cell Proteome Have Implications for Anti-Cancer Therapy

Julien Racle, Céline Hernández

The molecular chaperone Hsp90-dependent proteome represents a complex protein network of critical biological and medical relevance. Known to associate with proteins with a broad variety of functions termed clients, Hsp90 maintains key essential and oncogen ...

Public Library of Science2013