Transformation by homeobox genes can be mediated by selective transcriptional repression.
Altered transcription is a recurrent theme in the field of cancer biology. But despite the central role of transcription in transformation, little is known about the mechanism by which dominant nuclear oncogenes induce malignancies. Homeobox family proteins are prominent examples of transcriptional regulators which control development and can function as oncogenes. Here we explore the molecular basis for transformation by this class of regulators using Oct-2 and Oct-1. We show that the DNA binding POU domains of these proteins are selective and sequence-specific transcriptional repressors that produce malignant lymphomas when they are expressed in T cells of transgenic mice. Mutagenesis experiments identified a specific set of promoters, those containing octamer regulatory elements, as the targets for transformation by selective inhibition of gene expression.
Qin
X F
XF
Laboratory of Molecular Immunology, Howard Hughes Medical Institute, Rockfeller University.
Luo
Y
Y
Suh
H
H
Wayne
J
J
Misulovin
Z
Z
Roeder
R G
RG
Nussenzweig
M C
MC
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D005801:Genes, Homeobox / Q000235:genetics*; D051863:Host Cell Factor C1; D016399:Lymphoma, T-Cell / Q000209:etiology / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D050811:Octamer Transcription Factor-1; D050813:Octamer Transcription Factor-2; D011485:Protein Binding / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; C497693:Hcfc1 protein, mouse; D051863:Host Cell Factor C1; D050811:Octamer Transcription Factor-1; D050813:Octamer Transcription Factor-2; C494166:Pou2f1 protein, mouse; C489206:Pou2f2 protein, mouse; D014157:Transcription Factors