Altered cytoplasmic/nuclear distribution of the c-myc protein in differentiating ML-1 human myeloid leukemia cells

Cell Growth Differ. 1993 May;4(5):349-57.

Abstract

The c-myc gene is thought to play a role in cell proliferation and differentiation; for example, constitutive expression of an exogenously introduced c-myc gene can inhibit differentiation in hematopoietic cell lines. Expression of the endogenous c-myc gene has now been monitored during the differentiation, and associated loss of proliferation, of ML-1 human myeloblastic leukemia cells: c-myc mRNA remains detectable, at decreased levels, during differentiation along the monocyte/macrophage pathway induced with 12-O-tetradecanoylphorbol-13-acetate. c-myc protein also remains present, at undiminished levels, in mature, nonproliferative cells (assessed by immunoblotting and flow cytometry). The protein is, however, readily detectable in the cytoplasm of 12-O-tetradecanoylphorbol-13-acetate-induced cells, and some of this cytoplasmic c-myc exhibits a shift in electrophoretic mobility compared to the predominantly nuclear c-myc in uninduced cells. Furthermore, although c-myc protein continues to be synthesized in the mature cells (assessed by metabolic labeling/immunoprecipitation), loss of the protein from the cytoplasm and accumulation in the nucleus are slowed (assessed by pulse-chase metabolic labeling). These findings suggest that, during the 12-O-tetradecanoylphorbol-13-acetate-induced differentiation and loss of proliferation of ML-1 cells, c-myc protein is regulated through alterations that affect its cytoplasmic/nuclear distribution rather than its total cellular content.

Publication types

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

MeSH terms

  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Nucleus / chemistry*
  • Cytoplasm / chemistry*
  • Humans
  • Leukemia, Myeloid / metabolism*
  • Leukemia, Myeloid / pathology
  • Nuclear Proteins / analysis*
  • Proto-Oncogene Proteins c-myc / analysis*
  • Tetradecanoylphorbol Acetate
  • Tumor Cells, Cultured

Substances

  • Nuclear Proteins
  • Proto-Oncogene Proteins c-myc
  • Tetradecanoylphorbol Acetate