title: DEC1 is a downstream target of TGF-beta with sequence-specific transcriptional repressor activities.
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.
authors.affiliation: The Howard Hughes Medical Institute and The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Medical Institutions, 1650 Orleans Street, Baltimore, MD 21231, USA.
authors.forename: Leigh
authors.initials: L
authors.lastname: Zawel
authors.forename: Jian
authors.initials: J
authors.lastname: Yu
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Torrance
authors.forename: Sanford
authors.initials: S
authors.lastname: Markowitz
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Kinzler
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
authors.forename: Shibin
authors.initials: S
authors.lastname: Zhou
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002460:Cell Line; D015179:Colorectal Neoplasms; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018390:Gene Targeting; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta; D012097:Repressor Proteins; D016212:Transforming Growth Factor beta; C107989:BHLHE40 protein, human; C491539:Bhlhe40 protein, mouse