Basic mutant Max reverses a c-Myc block to differentiation
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- Published online on: January 1, 1996 https://doi.org/10.3892/or.3.1.141
- Pages: 141-146
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Abstract
Murine erythroleukemia (MEL) cells overexpressing a transfected c-myc gene are blocked in their ability to undergo inducer-mediated differentiation, whereas overexpression of a transfected max gene mutated within the basic region (bm-max) accelerates differentiation. Based on these findings, we cotransfected MEL cells with plasmids which express human c-Myc constitutively and bm-Max in a zinc-inducible manner. Competition of endogenous proteins for binding to bm-Max can be considered negligible in cells expressing such high constitutive levels of c-Myc. Thus, this system provides a cell culture model for studying Myc:Max complex formation and its effect on erythroid differentiation. Clones expressing high levels of c-Myc and low levels of bm-Max are blocked in their ability to undergo N,N'-hexamethylene bisacetamide (HMBA)-mediated differentiation, presumably due to a preponderance of growth-promoting Myc:Max complexes. However, increased expression of bm-Max, in these clones, allows differentiation to occur by decreasing the levels of functional Myc:Max complexes. Although the exogenously expressed c-Myc and bm-Max associate in vivo, the basic region mutation in bm-Max abolishes the binding of Myc:bm-Max complexes to the specific E-box consensus sequence. We demonstrate that this sequestering of c-Myc by bm-Max reverses the c-Myc block to differentiation.