Chemical Strike against a Dominant-Inherited MUC1-Frameshifted Protein Associated with Progressive Kidney Disease

Trends Mol Med. 2019 Oct;25(10):821-823. doi: 10.1016/j.molmed.2019.08.011. Epub 2019 Sep 11.

Abstract

In a recent paper by Dvela-Levitt et al., chemical screening using an immunofluorescent assay identified a compound that caused removal of a dominant-inherited misfolded secretory protein, mucin1-frameshifted, from an intracellular location in immortalized renal epithelial cells of a patient affected with progressive medullary cystic kidney disease. This illustrates the power of chemical screening at the cellular level to address specific proteinopathies and the utility of such compounds to illuminate novel cellular pathways that can clear toxic proteins.

MeSH terms

  • Animals
  • Drug Evaluation, Preclinical
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / genetics
  • Endoplasmic Reticulum / metabolism
  • Frameshifting, Ribosomal* / drug effects
  • Humans
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney Diseases, Cystic / drug therapy
  • Kidney Diseases, Cystic / genetics
  • Kidney Diseases, Cystic / metabolism*
  • Kidney Diseases, Cystic / physiopathology
  • Mice
  • Mucin-1 / chemistry*
  • Mucin-1 / genetics
  • Mucin-1 / metabolism
  • Protein Folding / drug effects
  • Unfolded Protein Response / drug effects

Substances

  • Mucin-1