期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:1993
卷号:90
期号:7
页码:2739-2743
DOI:10.1073/pnas.90.7.2739
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要:Myc proteins are basic helix-loop-helix/leucine-zipper proteins that bind to specific DNA sequences. In vivo, Myc proteins have been found associated with Max, another basic helix-loop-helix/leucine-zipper protein. However, it is not known to what extent the dimerization of Myc with Max is required for the manifestation of the Myc-induced phenotype. To investigate this, we constructed a dominant-negative mutant of Max, named dMax, that inhibits sequence-specific DNA binding of Myc proteins. Using a rat neuroblastoma model system, we show that dMax reverts N-Myc-induced changes in cellular gene expression. A control mutant of dMax that contains a proline residue in the leucine-zipper region was unable to bind to N-Myc and did not revert the N-Myc-induced changes in cellular gene expression. These data support the hypothesis that N-Myc affects neuroblastoma gene expression through the formation of a DNA-binding heterodimeric complex with Max in vivo.