Gene-target recognition among members of the myc superfamily and implications for oncogenesis.
Myc and Mad family proteins regulate multiple biological processes through their capacity to influence gene expression directly. Here we show that the basic regions of Myc and Mad proteins are not functionally equivalent in oncogenesis, have separable E-box-binding activities and engage both common and distinct gene targets. Our data support the view that the opposing biological actions of Myc and Mxi1 extend beyond reciprocal regulation of common gene targets. Identification of differentially regulated gene targets provides a framework for understanding the mechanism through which the Myc superfamily governs the growth, proliferation and survival of normal and neoplastic cells.
O'Hagan
R C
RC
Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Schreiber-Agus
N
N
Chen
K
K
David
G
G
Engelman
J A
JA
Schwab
R
R
Alland
L
L
Thomson
C
C
Ronning
D R
DR
Sacchettini
J C
JC
Meltzer
P
P
DePinho
R A
RA
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D016271:Proto-Oncogene Proteins c-myc / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014162:Transfection; D025521:Tumor Suppressor Proteins
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D016271:Proto-Oncogene Proteins c-myc; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C079439:MXD1 protein, human; C079440:MXI1 protein, human; C499479:Mad protein, mouse; C512788:Mxi1 protein, mouse