The Mad and Myc basic domains are functionally equivalent.
The Myc/Max/Mad family of transcription factors plays a fundamental role in the regulation of cell proliferation, oncogenic transformation, and cell differentiation. However, it remains unclear whether different heterodimers, such as Myc/Max and Mad/Max, recognize the same or different target genes in vivo. We show by chromatin immunoprecipitation that Myc target genes are also recognized by Mad1 in differentiated HL60 cells. We also substituted the complete basic region of Myc for the corresponding region of Mad. Wild-type c-Myc was then compared with c-Myc(Mad-BR) in oncogenic transformation, regulation of cell proliferation, induction of apoptosis, activation of chromosomal gene expression, and direct binding to chromosomal sites by chromatin immunoprecipitation. We find that the wild-type c-Myc and c-Myc/MadBR proteins have indistinguishable biological activity and target gene recognition in vivo. These data are consistent with a model in which Myc and Mad regulate a common set of target genes.
Nikiforov
Mikhail A
MA
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
Popov
Nikita
N
Kotenko
Iulia
I
Henriksson
Marie
M
Cole
Michael D
MD
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000502:physiology; D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D018922:HL-60 Cells; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D012097:Repressor Proteins
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D017931:DNA Primers; D004268:DNA-Binding Proteins; C079439:MXD1 protein, human; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins