A novel RP2 missense mutation Q158P identified in an X-linked retinitis pigmentosa family impaired RP2 protein stability

Gene. 2019 Jul 30:707:86-92. doi: 10.1016/j.gene.2019.05.006. Epub 2019 May 6.

Abstract

Retinitis pigmentosa (RP) is the most common form of inherited retinal degenerative diseases. X-linked RP accounts for nearly 15% of all RP cases. In this study, we identified a novel RP2 missense mutation Q158P in a Chinese XLRP family. The RP2 Q158P mutation located in the RP2 TBCC domain and obviously destabilized RP2 protein in ARPE-19 cells. The proteasome inhibitor MG132 could restore the RP2 Q158P protein levels. Meanwhile, lower doses of bortezomib and carfilzomib, another two proteasome inhibitors that have been approved in multiple myeloma clinical therapy, also could rescue the RP2 Q158P protein levels. The ubiquitination of RP2 Q158P protein obviously increased when compared with wild type RP2 protein. Our findings broadened the spectrum of RP2 mutations and may contribute a better understanding of the molecular mechanism of XLRP.

Keywords: Mutation; Proteasome; Protein stability; RP2; Retinitis pigmentosa.

MeSH terms

  • Cell Line
  • China
  • DNA Mutational Analysis
  • Eye Proteins / chemistry*
  • Eye Proteins / genetics*
  • Female
  • GTP-Binding Proteins
  • Genetic Diseases, X-Linked / genetics*
  • Humans
  • Intracellular Signaling Peptides and Proteins / chemistry*
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Male
  • Membrane Proteins / chemistry*
  • Membrane Proteins / genetics*
  • Models, Molecular
  • Mutation, Missense*
  • Pedigree
  • Protein Domains
  • Protein Stability
  • Retinitis Pigmentosa / genetics*
  • Sequence Analysis, DNA

Substances

  • Eye Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • RP2 protein, human
  • GTP-Binding Proteins