Cell Growth & Differentiation, Vol 4, Issue 5 349-357, Copyright © 1993 by American Association of Cancer Research

ARTICLES

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

RW Craig, HL Buchan, CI Civin and MB Kastan
Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.

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.

This article has been cited by other articles:

				J. Niklinski, G. Claassen, C. Meyers, M. A. Gregory, C. J. Allegra, F. J. Kaye, S. R. Hann, and M. Zajac-Kaye Disruption of Myc-Tubulin Interaction by Hyperphosphorylation of c-Myc during Mitosis or by Constitutive Hyperphosphorylation of Mutant c-Myc in Burkitt's Lymphoma Mol. Cell. Biol., July 15, 2000; 20(14): 5276 - 5284. [Abstract] [Full Text]

				B. M. Iritani and R. N. Eisenman c-Myc enhances protein synthesis and cell size during B lymphocyte development PNAS, November 9, 1999; 96(23): 13180 - 13185. [Abstract] [Full Text] [PDF]

				H. J. Okano, W.-Y. Park, J. P. Corradi, and R. B. Darnell The cytoplasmic Purkinje onconeural antigen cdr2 down-regulates c-Myc function: implications for neuronal and tumor cell survival Genes & Dev., August 15, 1999; 13(16): 2087 - 2097. [Abstract] [Full Text]

				P.J. Hurlin, D.E. Ayer, C. Grandori, and R.N. Eisenman The Max Transcription Factor Network: Involvement of Mad in Differentiation and an Approach to Identification of Target Genes Cold Spring Harb Symp Quant Biol, January 1, 1994; 59(0): 109 - 116. [Abstract] [PDF]

				D E Ayer and R N Eisenman A switch from Myc:Max to Mad:Max heterocomplexes accompanies monocyte/macrophage differentiation. Genes & Dev., November 1, 1993; 7(11): 2110 - 2119. [Abstract] [PDF]