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PMID: 9371770 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Myc represses transcription of the growth arrest gene gas1.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 94 ·No. 24 ·1997-11-25 ·Pages 12886-91

Lee TC, Li L, Philipson L, Ziff EB

Abstract

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.

MeSH Terms
3T3 Cells Animals Cell Cycle Proteins Cell Line GPI-Linked Proteins Gene Expression Regulation Membrane Proteins/genetics Mice Proto-Oncogene Proteins c-myc/metabolism RNA, Messenger/genetics,metabolism Rats Transcription, Genetic
Chemicals
Cell Cycle Proteins GAS1 protein, human GPI-Linked Proteins Gas1 protein, mouse Gas1 protein, rat Membrane Proteins Proto-Oncogene Proteins c-myc RNA, Messenger
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Lee T C
Howard Hughes Medical Institute, Department of Biochemistry, New York University Medical Center, NY 10016, USA.
Li L
Philipson L
Ziff E B
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.94.24.12886
Published
1997-11-25
Pages
12886-91
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC24233
Subset
IM
Grants
NCI NIH HHS · K12 CA001713 · United States
NIA NIH HHS · R01 AG013620 · United States
NCI NIH HHS · CA-01713 · United States
NIA NIH HHS · R01 AG13620 · United States
External Links
PubMed source DOI: 10.1073/pnas.94.24.12886 PMC Full Text View journal details
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