Altered cytoplasmic/nuclear distribution of the c-myc protein in differentiating ML-1 human myeloid leukemia cells.
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.
Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
R W
RW
Craig
H L
HL
Buchan
C I
CI
Civin
M B
MB
Kastan
D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002467:Cell Nucleus / Q000737:chemistry*; D003593:Cytoplasm / Q000737:chemistry*; D006801:Humans; D007951:Leukemia, Myeloid / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000032:analysis*; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis*; D013755:Tetradecanoylphorbol Acetate; D014407:Tumor Cells, Cultured
D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D013755:Tetradecanoylphorbol Acetate