The Antiangiogenic Insulin Receptor Substrate-1 Antisense Oligonucleotide Aganirsen Impairs AU-Rich mRNA Stability by Reducing 14-3-3β–Tristetraprolin Protein …

S Colin, B Darné, A Kadi, A Ferry, M Favier… - The Journal of …, 2014 - Elsevier
Increased inflammation and aberrant angiogenesis underlie psoriasis. Here, we report that
the inhibition of insulin receptor substrate-1 (IRS-1) expression with aganirsen resulted in a
dose-dependent reduction (P< 0.0001) in IRS-1 protein in the cytoplasm, while IRS-1 protein
remained quantitatively unchanged in the perinuclear environment. Aganirsen induced a
dose-dependent increase in serine-phosphorylated IRS-1 in the soluble perinuclear-nuclear
fraction, inducing IRS-1–14-3-3β protein association (P< 0.001), thereby impairing 14-3-3β …