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PMID: 11880636 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

DEC1 is a downstream target of TGF-beta with sequence-specific transcriptional repressor activities.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 99 ·No. 5 ·2002-03-05 ·Pages 2848-53

Zawel L, Yu J, Torrance CJ, Markowitz S, Kinzler KW, Vogelstein B, Zhou S

Abstract

To identify genes that mediate transforming growth factor-beta (TGF-beta) signaling, a colorectal cancer cell line that was sensitive to the growth inhibitory effects of this cytokine was created. We then determined the global gene expression profiles of these cells, and those of HaCaT human keratinocytes, in the presence and absence of TGF-beta. Of the several genes identified in this screen, DEC1 was of particular note in light of the rapidity and consistency of its induction and its potential biochemical activities. We identified a consensus DNA-binding site for DEC1 and showed that DEC1 could repress the transcription of a reporter containing this binding site in its promoter. Finally, both alleles of the DEC1 locus in HaCaT cells were inactivated through targeted homologous recombination. This approach revealed that DEC1 induction was not required for the growth inhibition mediated by TGF-beta in this line. However, DEC1 may function in concert with other signaling components to mediate certain biologic effects of TGF-beta.

MeSH Terms
Animals Basic Helix-Loop-Helix Transcription Factors Cell Line Colorectal Neoplasms DNA-Binding Proteins/genetics,metabolism Gene Targeting Homeodomain Proteins/genetics,metabolism Humans Mice Mice, Nude Protein Serine-Threonine Kinases Receptor, Transforming Growth Factor-beta Type II Receptors, Transforming Growth Factor beta/genetics Repressor Proteins/genetics,metabolism Transcription, Genetic Transforming Growth Factor beta/metabolism Tumor Cells, Cultured
Chemicals
BHLHE40 protein, human Basic Helix-Loop-Helix Transcription Factors Bhlhe40 protein, mouse DNA-Binding Proteins Homeodomain Proteins Receptors, Transforming Growth Factor beta Repressor Proteins Transforming Growth Factor beta Protein Serine-Threonine Kinases Receptor, Transforming Growth Factor-beta Type II
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Zawel Leigh
The Howard Hughes Medical Institute and The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Medical Institutions, 1650 Orleans Street, Baltimore, MD 21231, USA.
Yu Jian
Torrance Christopher J
Markowitz Sanford
Kinzler Kenneth W
Vogelstein Bert
Zhou Shibin
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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.261714999
Published
2002-03-05
Pages
2848-53
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC122436
Subset
IM
Grants
NCI NIH HHS · P50 CA062924 · United States
NCI NIH HHS · R37 CA043460 · United States
NCI NIH HHS · CA 43460 · United States
NCI NIH HHS · CA 62924 · United States
External Links
PubMed source DOI: 10.1073/pnas.261714999 PMC Full Text View journal details
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