REGULATION OF MURINE MAX (MYN) PARALLELS THE REGULATION OF C-MYC IN DIFFERENTIATING MURINE ERYTHROLEUKEMIA-CELLS

Max is a basic region-helix-loop-helix-leucine zipper protein that con sists of two major isoforms, p22 (long form, Max-L) and p21 (short for m, Max-S). These proteins are encoded by two [the 1.9- and the predomi nant 2.3-kilobase (kb) forms] of the five alternatively spliced max mR NA species. We now demonstrate that N,N'-hexamethylene bisacetamide-me diated differentiation of murine erythroleukemia cells leads to a patt ern 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 i n 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. Fu rthermore, unlike myc, the overexpression of which prevents differenti ation, elevated max levels merely delay differentiation. Coincident wi th this is a delay in the second decline of c-myc mRNA. In N,N'-hexame thylene bisacetamide-induced cells blocked from differentiating by ove rexpression of c-, N- or L-myc, myn mRNA expression is constitutive. T hese findings suggest that