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Aldo-keto reductase 1C3 (AKR1C3, EC 1.1.1.188) metabolises steroid hormones, prostaglandins and xenobiotics, and activates the dinitrobenzamide mustard prodrug PR-104A by reducing it to hydroxylamine PR-104H. Here, we describe a functional assay for AKR1C3 in cells using the fluorogenic probe coumberone (a substrate for all AKR1C isoforms) in conjunction with a specific inhibitor of AKR1C3, the morpholylurea...
In osteoblasts, Integrin-Linked Kinase (ILK)-dependent phosphorylation of the cJUN transcriptional coactivator, αNAC, induces the nuclear accumulation of the coactivator and potentiates cJUN-dependent transcription. Mutation of the ILK phosphoacceptor site within the αNAC protein leads to cytoplasmic retention of the coactivator and cell-autonomous increases in osteoblastic activity. In order to gain...
Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder that is associated with a variety of manifestations, including orthopedic complications such as scoliosis and tibial pseudarthrosis. Orthopedic management of these skeletal complications is rendered more challenging due to a lack of standardized adjunctive pharmacotherapies. NF1 leads to disruption of the canonical Ras/Raf-1/MEK/ERK...
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