Transfected wild-type and mutant max regulate cell growth and differentiation of murine erythroleukemia cells.
Max protein forms specific DNA-binding dimeric complexes with itself and with proteins of the c-myc gene family. A large volume of data has accumulated on the role of the c-myc proto-oncogene in cell proliferation, differentiation and tumorigenesis. To elucidate the role of max in regulating c-myc functions and the effect of both proteins on cell proliferation and differentiation, we transfected murine erythroleukemia (MEL) cells with a full-length wild-type (wt) human max gene and a mutant containing a double point mutation in the basic region (bm), which abolishes specific DNA binding. All clones expressing wt-max grow slowly, and the process of inducer-mediated differentiation is delayed. Furthermore, cells transfected with the mutated max exhibit growth retardation, accumulation in the G0/G1 phase of the cell cycle and spontaneous differentiation. Our findings are consistent with a model in which a large excess of wt-Max in the cells enhances the formation of Max-Max growth-suppressor complexes, while elevated bm-Max deprives the cell of growth-promoting Myc-Max heterodimers in a dominant-negative manner, presumably by inactivating endogenous Myc and Max.
Cogliati
T
T
NCI-Navy Medical Oncology Branch, NIH, Bethesda, Maryland 20889-5105.
Dunn
B K
BK
Bar-Ner
M
M
Cultraro
C M
CM
Segal
S
S
D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D002453:Cell Cycle; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D016259:Genes, myc; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D000090063:Proto-Oncogene Mas; D014157:Transcription Factors; D014162:Transfection; D014407:Tumor Cells, Cultured; D015032:Zinc / Q000494:pharmacology
D000081:Acetamides; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; C067850:Myc associated factor X; D000090063:Proto-Oncogene Mas; D014157:Transcription Factors; C068422:Max protein, mouse; D015032:Zinc; C014026:hexamethylene bisacetamide