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 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.
Dunn
B K
BK
NCI-Navy Medical Oncology Branch, NIH, Bethesda, Maryland 20889.
Cogliati
T
T
Cultraro
C M
CM
Bar-Ner
M
M
Segal
S
S
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D016259:Genes, myc; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics* / Q000473:pathology; D051379:Mice; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D014162:Transfection; D014407:Tumor Cells, Cultured
D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger