• Given its high frequency it is not

  2019-10-15

  

  Given its high frequency, it is not surprising that different strategies have been developed to restore the sensitivity of EGFR T790M-mutant gap 26 mass to EGFR inhibition. To date, several different strategies have been evaluated in both preclinical and clinical models, but only few have been prov

• Similar to EGFR another receptor tyrosine kinase RTK

  2019-10-15

  

  Similar to EGFR, another receptor tyrosine kinase (RTK), fibroblast growth factor receptor 4 (FGFR4), is gaining attention in the lung cancer setting. The protein expression of this receptor has been recently associated with a negative impact on lung cancer prognosis, supporting the idea that FGFR4

• br Genomic actions in the breast br

  2019-10-14

  

  Genomic actions in the breast Conclusion Clinical studies suggest that progesterone and/or progestins may play a decisive role in the development of breast cancer in women using hormone therapy or oral contraceptives [3], [4]. However, this data are controversial to most experimental investiga

• Thus the understanding of the various mechanisms of action o

  2019-10-14

  

  Thus, the understanding of the various mechanisms of action of estrogen and SERMs is an important medical challenge and could help to develop an “ideal” SERM, preserving the beneficial effects of estrogen in the bone and urogenital system, and reducing the unwanted side effects, mainly increased ris

• One possibility to differentiate between the

  2019-10-14

  

  One possibility to differentiate between the two failure modes, and also to identify the corresponding characteristics of the resulting fracture surface, is a series of FNCT measurements with varying nominal (initial) stress. The dependence of the observed time to failure tf on the actual stress cha

• Another milestone in the field is the de

  2019-10-14

  

  Another milestone in the field is the de novo discovery of EPAC2 and EPAC1 specific inhibitors through fluorescence-based HTS assays. Due to the excellent EPAC/PKA selectivity of Pertussis Toxin , it has been widely applied as a useful chemical probe to discriminate EPAC related signaling pathways a

• br Structure of USP Schematic representation of the USP doma

  2019-10-14

  

  Structure of USP7 Schematic representation of the USP7 domain architecture is shown in Fig. 3B. USP7 is a 135 kDa protein that consists of seven domains, including the N-terminal TRAF-like (Tumor necrosis factor Receptor–Associated Factor) domain, followed by the catalytic core domain and the fiv

• br Ubiquitin Capture by the

  2019-10-14

  

  Ubiquitin Capture by the Mobile APC11 RING Domain Contributes to Processive Substrate Ubiquitylation Although the rules of Ub-mediated proteolysis are only beginning to emerge, the rate and order in which different APC/C substrates are degraded during the JQ1 correlates with processivity of their

• Another pathway that requires proper DUB

  2019-10-14

  

  Another pathway that requires proper DUB recruitment is the DNA damage response (DDR). After ultraviolet (UV)-induced DNA damage, monoubiquitylated proliferating cell nuclear antigen (PCNA) mediates signaling that leads to repair. The DUB complex USP1/USP1-associated factor 1 (UAF1) deubiquitylates

• br Molecular modeling study Molecular modeling study was

  2019-10-14

  

  Molecular modeling study Molecular modeling study was essentially needed to understand and interpret the DHFR inhibitory pattern of this new class of compounds. Computational docking is an algorithm designed to estimate two main terms. The first is to determine the suitable position and the orien

• As a basis for the DDR substrate identification approach det

  2019-10-14

  

  As a basis for the DDR1 substrate identification approach detailed below, we first set out to perform 2D-gel electrophoresis with lysates isolated from collagen-stimulated human breast cancer MDA-MB-231 Obeticholic Acid overexpressing DDR1 (b-isoform). This allowed us to determine whether DDR1 is no

• In the pleural exudates which

  2019-10-14

  

  In the pleural exudates, which reflect the in vivo conditions, the concentrations of CysLTs and PGE2 were quite similar. However, when cancer NECA were cultured for 24 h, both analyses of cell culture medium and cell incubations with Ca2+ ionophore showed low levels of CysLTs. In contrast, the pred

• br Introduction br Conclusion br Acknowledgments and

  2019-10-14

  

  Introduction Conclusion Acknowledgments and Funding Introduction Reversible protein phosphorylation is an important post-translational modification of proteins regulating many processes in the cell. Approximately one third of the cellular proteome is phosphorylated, and several sites are

• Although CK phosphorylated Msn as well as

  2019-10-14

  

  Although CK2 phosphorylated Msn4 as well as Msn2 (Fig. 1A), the two CK2-dependent phosphorylation sites in Msn2 are not conserved in Msn4. Thus, Msn2 and Msn4 might be differently regulated by CK2-dependent phosphorylation. Msn2 and Msn4, which have 41% identity and similarity in size and amino sali

• Although several genomic technologies including the generati

  2019-10-14

  

  Although several genomic technologies, including the generation of ERRγ-specific knockout mice, have revealed that ERRγ plays a pivotal role in cellular bioenergetics [1], its involvement in other metabolic pathways has been appreciated only recently. Therefore, we highlight recent findings on the r

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