Publications by authors named "Loyse M Felber"
The epidermal growth factor receptor (EGFR) plays a central role in cell life by controlling processes such as growth or proliferation. This receptor is commonly overexpressed in a number of epithelial malignancies and its upregulation is often associated with an aggressive phenotype of the tumor. Thus, targeting of EGFR represents a very promising challenge in oncology, and antibodies raised against this receptor have been investigated as potential antitumor agents.
View Article and Find Full Text PDFThe reactive center loop (RCL) of serpins plays an essential role in the inhibition mechanism acting as a substrate for their target proteases. Changes within the RCL sequence modulate the specificity and reactivity of the serpin molecule. Recently, we reported the construction of alpha1-antichymotrypsin (ACT) variants with high specificity towards human kallikrein 2 (hK2) [Cloutier SM, Kündig C, Felber LM, Fattah OM, Chagas JR, Gygi CM, Jichlinski P, Leisinger HJ & Deperthes D (2004) Eur J Biochem271, 607-613] by changing amino acids surrounding the scissile bond of the RCL and obtained specific inhibitors towards hK2.
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- The KLK14 gene is a newly discovered member of the human kallikrein family, which consists of 15 serine protease genes, primarily found in prostate and endocrine tissues, but its exact function remains unclear.
- Studies indicate that KLK14 expression is elevated in prostate and breast cancer tissues, with higher levels linked to more aggressive tumors.
- Using phage-display technology, researchers identified specific substrates for KLK14, revealing its dual activity (trypsin- and chymotrypsin-like) and showed it can effectively hydrolyze important extracellular matrix proteins like laminin alpha-5 and collagen IV.
Article Synopsis
- A protease is an enzyme that breaks down peptide bonds, and characterizing it involves identifying peptide sequences, measuring activity, and determining kinetic parameters.
- New biological substrates using fluorescent proteins (CFP and YFP) have been created for in vivo detection of protease activity, offering an alternative to traditional chemical substrates for in vitro testing.
- The study optimizes conditions for producing the CFP-YFP fusion protein in E. coli, finding optimal FRET activity at specific pH, salt concentration, and temperature while demonstrating the system's resistance to nonspecific proteolysis and measuring substrate specificity through kinetic analysis.
The reactive site loop of serpins undoubtedly defines in part their ability to inhibit a particular enzyme. Exchanges in the reactive loop of serpins might reassign the targets and modify the serpin-protease interaction kinetics. Based on this concept, we have developed a procedure to change the specificity of known serpins.
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