Cell Growth & Differentiation, Vol 5, Issue 8 847-854, Copyright © 1994 by American Association of Cancer Research
Regulation of murine Max (Myn) parallels the regulation of c-Myc in differentiating murine erythroleukemia cells
BK Dunn, T Cogliati, CM Cultraro, M Bar-Ner and S Segal
NCI-Navy Medical Oncology Branch, NIH, Bethesda, Maryland 20889.
Max is a basic region-helix-loop-helix-leucine zipper protein that consists
of two major isoforms, p22 (long form, Max-L) and p21 (short form, Max-S).
These proteins are encoded by two [the 1.9- and the predominant
2.3-kilobase (kb) forms] of the five alternatively spliced max mRNA
species. We now demonstrate that N,N'-hexamethylene bisacetamide-mediated
differentiation of murine erythroleukemia cells leads to a pattern of
biphasic down-regulation of the 1.9- and the 2.3-kb myn (murine max) mRNAs
that closely parallels that which occurs for myc mRNA. In contrast, the
p22/Myn-L and p21/Myn-S protein isoforms down-regulate in monophasic
fashion. Unlike the short-lived myc mRNA, the myn message is quite stable.
However, its half-life of 3-6 h is still consistent with the biphasic
down-regulation that accompanies differentiation. Furthermore, unlike myc,
the overexpression of which prevents differentiation, elevated max levels
merely delay differentiation. Coincident with this is a delay in the second
decline of c-myc mRNA. In N,N'-hexamethylene bisacetamide-induced cells
blocked from differentiating by overexpression of c-, N- or L-myc, myn mRNA
expression is constitutive. These findings suggest that myn may also be
involved in differentiation.