Myc represses transcription of the growth arrest gene gas1.
Cell proliferation is regulated by the induction of growth promoting genes and the suppression of growth inhibitory genes. Malignant growth can result from the altered balance of expression of these genes in favor of cell proliferation. Induction of the transcription factor, c-Myc, promotes cell proliferation and transformation by activating growth promoting genes, including the ODC and cdc25A genes. We show that c-Myc transcriptionally represses the expression of a growth arrest gene, gas1. A conserved Myc structure, Myc box 2, is required for repression of gas1, and for Myc induction of proliferation and transformation, but not for activation of ODC. Activation of a Myc-estrogen receptor fusion protein by 4-hydroxytamoxifen was sufficient to repress gas1 gene transcription. These findings suggest that transcriptional repression of growth arrest genes, including gas1, is one step in promotion of cell growth by Myc.
Lee
T C
TC
Howard Hughes Medical Institute, Department of Biochemistry, New York University Medical Center, NY 10016, USA.
Li
L
L
Philipson
L
L
Ziff
E B
EB
D016475:3T3 Cells; D000818:Animals; D018797:Cell Cycle Proteins; D002460:Cell Line; D058851:GPI-Linked Proteins; D005786:Gene Expression Regulation; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D014158:Transcription, Genetic
D018797:Cell Cycle Proteins; C096192:GAS1 protein, human; D058851:GPI-Linked Proteins; C501180:Gas1 protein, mouse; C501181:Gas1 protein, rat; D008565:Membrane Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger