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Somatic activation of the K-ras oncogene causes early onset lung cancer in mice
It is shown that mice carrying mutations in the tumour suppressor gene p53 were highly predisposed to a range of tumour types, predominantly early onset lung cancer.
Epoxide electrophiles as activity-dependent cysteine protease profiling and discovery tools.
A simple and flexible method for functionally identifying cysteine proteases while simultaneously tracking their relative activity levels in crude protein mixtures is created and information obtained from libraries of affinity probes provides a rapid method for obtaining detailed functional information without the need for prior purification/identification of targets.
K-ras is an essential gene in the mouse with partial functional overlap with N-ras.
Mammalian ras genes are thought to be critical in the regulation of cellular proliferation and differentiation and are mutated in approximately 30% of all human tumors. However, N-ras and H-ras are
Distinct Protein Classes Including Novel Merozoite Surface Antigens in Raft-like Membranes of Plasmodium falciparum*
The proteome of gradient-purified detergent-resistant membranes of mature blood-stage parasites are greatly enriched in GPI-anchored proteins and their putative interacting partners, providing new opportunities for understanding both erythrocyte invasion and anti-parasite immunity.
Cathepsin cysteine proteases are effectors of invasive growth and angiogenesis during multistage tumorigenesis.
Gene expression profiling of pancreatic islet tumors in a mouse model of cancer revealed upregulation of cathepsin cysteine proteases, encouraging consideration of this protease family as a therapeutic target in human cancers.
Cathepsin V, a Novel and Potent Elastolytic Activity Expressed in Activated Macrophages*
It is demonstrated that macrophages express a third elastolytic cysteine protease, cathepsin V, which exhibits the most potent elastase activity yet described among human proteases and that cathePSin V is present in atherosclerotic plaque specimens.
A Role for the Protease Falcipain 1 in Host Cell Invasion by the Human Malaria Parasite
A specific role for falcipain 1 in host cell invasion is demonstrated and a potential new target for antimalarial therapeutics is established.
Chemical Approaches for Functionally Probing the Proteome*
A functional proteomic methodology that makes use of chemically reactive fluorescent probes to profile and identify enzymes in complex mixtures by virtue of their catalytic activity, which allows the rapid identification of potential drug targets and small molecule lead compounds targeted to them.
Defining a Link between Gap Junction Communication, Proteolysis, and Cataract Formation*
A role for α3 gap junctions in maintaining calcium homeostasis is established that in turn is required to control activity of the calcium-dependent cysteine protease Lp82, shown here to be a key initiator of the process of cataractogenesis.
Substrate Profiling of Cysteine Proteases Using a Combinatorial Peptide Library Identifies Functionally Unique Specificities*
The substrate specificities of papain-like cysteine proteases and human cathepsins L, V, K, S, F, B, and five proteases of parasitic origin were studied using a completely diversified positional scanning synthetic combinatorial library.