A long-range foresight for the medical application of apoptosis specifically induced by Dd-MRP4, Dictyostelium mitochondrial ribosomal protein S4, to cancer therapy

Biomolecules. 2015 Feb 10;5(1):113-20. doi: 10.3390/biom5010113.

Abstract

Apoptosis (programmed cell death) is regarded as ultimate differentiation of the cell. We have recently demonstrated that a targeted delivery of Dd-MRP4 (Dictyostelium mitochondrial ribosomal protein S4) suppresses specifically the proliferation of the human cancer cells, by inducing their apoptotic cell death (Chida et al., 2014, doi:10.1186/1475-2867-14-56). This amazing fact was discovered, simply based on the finding that Dd-MRP4 expression is absolutely required for transition of Dictyostelium cells from growth to differentiation (Chida et al., 2008, doi:10.1186/1471-2156-9-25; Maeda et al., 2013, doi:10.3390/biom3040943). Dd-MRP4 protein has quite unique structural characters, in that it is highly basic (pI: about 11.5) and interestingly has several nuclear-localization signals within the molecule. In this review, we introduce briefly the efficacy of several apoptosis-inducing substances reported thus far for cancer therapy, and speculate the possible mechanisms, by which apoptosis is specifically induced by Dd-MRP4, on the basis of its structural uniqueness. We also discuss several issues to be solved for the medical application of ectopically expressed Dd-MRP4 in human cancer cells.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Apoptosis*
  • Dictyostelium / cytology*
  • Humans
  • Mitochondria / metabolism*
  • Molecular Sequence Data
  • Neoplasms / genetics
  • Neoplasms / pathology*
  • Neoplasms / therapy*
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*
  • Ribosomal Proteins / chemistry
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / metabolism*

Substances

  • Protozoan Proteins
  • Ribosomal Proteins
  • ribosomal protein S4