Intrinsically disordered chromatin protein NUPR1 binds to the C-terminal region of Polycomb RING1B

• DOI: 10.1073/pnas.1619932114
• Publication Date: 2017-07-19T00:30:26Z
• Authors: Patricia Santofim...; Bruno Rizzuti; Ángel L. Pey; Philippe Soubeyran; Miguel Vidal; Raúl Urrutia; Juan L. Iovanna; José L. Neira
• Keywords: Intrinsically Disordered Proteins

Intrinsically disordered proteins (IDPs) are ubiquitous in eukaryotes, and they often associated with diseases humans. The protein NUPR1 is a multifunctional IDP involved chromatin remodeling the development progression of pancreatic cancer; however, details such functions unknown. Polycomb specific transcriptional cascades gene silencing. One complex Ring finger 1 (RING1). RING1 related to aggressive tumor features multiple cancer types. In this work we characterized interaction between paralogue RING1B vitro, silico, cellulo. occurred through C-terminal region (C-RING1B), an affinity low micromolar range (∼10 μM). binding NUPR1, mapped by NMR, was hydrophobic polypeptide patch at 30s its sequence, as pinpointed computational results site-directed mutagenesis Ala33. association C-RING1B wild-type also cellulo tested ligation assays; inhibited trifluoperazine, drug known hamper other proteins. Furthermore, Thr68Gln Ala33Gln/Thr68Gln mutants had reduction toward shown studies. This example well-folded partner because interacting unfolded. We hypothesize that plays active role carcinogenesis, together