Inhibitors of protein translocation across membranes of the secretory pathway: novel antimicrobial and anticancer agents

Cell Mol Life Sci. 2018 May;75(9):1541-1558. doi: 10.1007/s00018-017-2743-2. Epub 2018 Jan 5.

Abstract

Proteins routed to the secretory pathway start their journey by being transported across biological membranes, such as the endoplasmic reticulum. The essential nature of this protein translocation process has led to the evolution of several factors that specifically target the translocon and block translocation. In this review, various translocation pathways are discussed together with known inhibitors of translocation. Properties of signal peptide-specific systems are highlighted for the development of new therapeutic and antimicrobial applications, as compounds can target signal peptides from either host cells or pathogens and thereby selectively prevent translocation of those specific proteins. Broad inhibition of translocation is also an interesting target for the development of new anticancer drugs because cancer cells heavily depend on efficient protein translocation into the endoplasmic reticulum to support their fast growth.

Keywords: Endoplasmic reticulum; Protein translocation; Sec61; SecY; Signal peptide; Translocation inhibitor; Translocon.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Infective Agents / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Drug Discovery / methods*
  • Endoplasmic Reticulum / drug effects*
  • Endoplasmic Reticulum / metabolism
  • Humans
  • Models, Molecular
  • Molecular Targeted Therapy / methods
  • Neoplasms / drug therapy
  • Protein Sorting Signals / drug effects
  • Protein Transport / drug effects*

Substances

  • Anti-Infective Agents
  • Antineoplastic Agents
  • Protein Sorting Signals