Proteasome is a carrier to translocate doxorubicin from cytoplasm into nucleus

Life Sci. 1998;62(20):1853-60. doi: 10.1016/s0024-3205(98)00151-9.

Abstract

When an effective concentration of doxorubicin (DXR) was added into L1210 of a mouse leukemia cell line, DXR was rapidly distributed much more in the nuclei than in the other organelle within a few minutes. A [14C]DXR-binding fraction was obtained from the cytosol prepared from L1210 cells. The fraction was adsorbed to hydroxylapatite matrix and eluted from the matrix by 50-150 mM potassium phosphate buffer. The fraction showed high DXR-binding and Suc-Leu-Leu-Val-Tyr-MCA-degrading activity. The binding of [14C]DXR was inhibited by unlabeled DXR. Gel chromatography of the fraction with Sephacryl S-300 separated two fractions of high molecular weight (Peak I, approx. 750 kDa) and low molecular weight (Peak II). Peak I showed proteolytic activity. [14C]DXR-binding Peak I had much higher affinity to DNA-cellulose than [14C]DXR-binding Peak II. [14C]DXR-Peak I complex also was retained into the nuclei isolated from L1210 cells, temperature-dependently. These results suggest that a specific carrier to translocate DXR from cytoplasm into nucleus exists in L1210 cell and the carrier is proteasome.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / metabolism*
  • Biological Transport
  • Carrier Proteins / metabolism*
  • Cell Fractionation
  • Cell Nucleus / metabolism*
  • Chromatography, Gel
  • Chromatography, High Pressure Liquid
  • Cysteine Endopeptidases / metabolism*
  • Cytoplasm / metabolism*
  • Cytosol / metabolism
  • Doxorubicin / metabolism*
  • Leukemia L1210 / metabolism*
  • Mice
  • Multienzyme Complexes / metabolism*
  • Proteasome Endopeptidase Complex
  • Tumor Cells, Cultured

Substances

  • Antibiotics, Antineoplastic
  • Carrier Proteins
  • Multienzyme Complexes
  • Doxorubicin
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex