• At the cellular level TGF has been involved in the

  2019-11-14

  

  At the cellular level, TGF-β1 has been involved in the formation of invadosomes (Mandal et al., 2008, Varon et al., 2006). Invadosomes are actin-based structures involved in matrix degradation and cell invasion through metalloproteinases (MMP) activity (Linder et al., 2011). Invadosomes, constitutiv

• The IP R is a

  2019-11-14

  

  The IP3R is a ubiquitously expressed Ca2+-release channel from the ER, activated by IP3, produced upon cellular stimulation by hormones, growth factors or neurotransmitters. Three genes are coding for the IP3R and their gene products (IP3R1, IP3R2, IP3R3) assemble in functional homo- or heterotetram

• Methotrexate Dose response analysis Fig can be

  2019-11-14

  

  Dose response analysis (Fig. 2) can be performed on Methotrexate in culture, in tissue, in animals or even in patients. Many different responses can be measured, including mRNA levels, reporter gene activity, gene product (e.g. enzyme) activity or even physiological functions such as inhibition of o

• br In order to determine the physiological roles of

  2019-11-14

  

  In order to determine the physiological roles of WT (wild type) EWSR1, Dr. Lee\'s group established a conventional Ewsr1 KO mouse [38]. Since then, the Ewsr1 KO (−/−) mouse model has successfully been utilized to decipher many important in vivo roles of EWSR1 (Fig. 1). EWSR1 deficiency alters m

• The presence of a vicious cycle established between

  2019-11-14

  

  The presence of a “vicious cycle” established between tumor proliferation and paratumor osteolysis plays a crucial role in the development of primary bone tumors [53]. Cancer cells produce soluble factors that activate directly or indirectly via osteoblasts, osteoclast differentiation and maturation

• The development of novel approaches to study GPCR

  2019-11-14

  

  The development of novel approaches to study GPCR-mediated transactivation in live Sodium Phenylbutyrate is important, and this study describes a unique BRET-based quantification of Grb2 recruitment to the EGFR as a direct readout of GPCR-mediated transactivation. We have previously used the recrui

• The interface between the E ligase and the E enzyme

  2019-11-14

  

  The interface between the E3 ligase and the E2 enzyme can vary, and ZNF451 and SP-RING ligases stabilize this interaction via noncovalent binding to a scaffold SUMO (SUMOB) on the backside of the E2 (Cappadocia et al., 2015; Eisenhardt et al., 2015; Streich & Lima, 2016). By contrast, RanBP2 does no

• br Discussion and conclusion Ubiquitination and deubiquitina

  2019-11-14

  

  Discussion and conclusion Ubiquitination and deubiquitination have emerged as important mechanisms involved in p53 management. This review revealed that various DUBs can regulate p53 or p53-Mdm2-MdmX networks. Herein, we reviewed the current progress made toward elucidating the complexities in th

• The present study is a genetic association study using

  2019-11-14

  

  The present study is a genetic association study using the classic candidate gene approach. This method has been repeatedly criticized in the past to produce highly unreliably findings (e.g. Flint & Munafò, 2013). The alternative would be the conduction of a Cy7 carboxylic acid (non-sulfonated) wide

• In terms of its protease activity

  2019-11-13

  

  In terms of its protease activity, MME has a broad range of substrates being able to target glucagon, bradykinin, GLP1, and several other α-Bungarotoxin of circulating small molecules [25]. MME has been shown to target free insulin B-chain [32], although whether MME could target and degrade the ins

• The discoidin domain receptors DDR

  2019-11-13

  

  The discoidin domain receptors, DDR1 and DDR2, are receptor tyrosine kinases (RTKs) that are stimulated by collagen in the extracellular matrix (ECM). Unlike most other RTKs, they form ligand-independent stable dimers that are non-covalently linked. This ECM activation induces receptor phosphorylati

• br Advantages of modified proteins over unmodified

  2019-11-13

  

  Advantages of modified proteins over unmodified ones In contrast to small-molecule drugs, proteins are readily amenable to site-specific alterations through genetic engineering. In principle, therefore, it is possible to build in features that allow them to remain active for longer in the body an

• Most remarkably an essentially identical collagen

  2019-11-13

  

  Most remarkably, an essentially identical collagen-binding mode to DDR2 is employed by SPARC, an α-helical matricellular protein unrelated to DDR2 that also recognizes the GVMGFO motif in collagen (Giudici et al., 2008, Hohenester et al., 2008). The convergence of binding mechanisms suggests that th

• br Expression and Tissue Functions of DDRs The DDRs

  2019-11-13

  

  Expression and Tissue Functions of DDRs The DDRs are widely expressed in different tissues, both during development and in adult organisms. DDR1 mRNA is found in many tissues in mice and humans, with high levels in brain, lung, kidney, spleen, and placenta (Di Marco et al., 1993, Johnson et al.,

• The attachment of ubiquitin to RTKs such

  2019-11-13

  

  The attachment of ubiquitin to RTKs, such as EGFR, mediates efficient delivery through the endosome-lysosome system for proteolysis. In this way, RTK degradation enables cessation of signal transduction. A recent siRNA screen identified a number of USPs that can significantly modulate EGFR levels an

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