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Cited by 183

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Activation of the second promoter of the transforming growth factor-β1 gene by transforming growth factor-β1 and phorbol ester occurs through the same target sequences

Open access
Kim, S J, Denhez, F, Kim, K Y, Holt, J T, Sporn, M B, Roberts, A B·1989·Journal of Biological Chemistry

Abstract

Two distinct regions of the transforming growth factor-beta 1 (TGF-beta 1) promoter are responsive to autoregulation and activation by phorbol ester (12-O-tetradecanoylphorbol-13-acetate): sequences located between nucleotides -454 to -323 (first promoter) and between the two transcriptional start sites. We have now characterized in detail the induction of the second promoter (sequences between nucleotides + 1 to +271) of the TGF-beta 1 gene by both TGF-beta 1 and phorbol ester. By assaying progressively deleted mutations in the second promoter, we have found two regions responsible for the induction; each contains a phorbol ester-responsive element. In vitro transcription of the second promoter-chloramphenicol acetyltransferase chimeric genes using nuclear extracts of A-549 cells showed that deletion of the putative phorbol ester-responsive elements results in a 70-80% decrease in activity. DNase I footprinting and gel mobility shift assays showed that binding to an Sp1 site and the putative TRE elements are required for maximal expression of the second promoter region of the TGF-beta 1 gene. These results suggest that AP-1, which is capable of conferring phorbol ester or TGF-beta 1 responsiveness, is the major transcription factor involved in the second promoter-derived transcription of the TGF-beta 1 gene.

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Metadata

Authors
Kim, S. J., Denhez, F., Kim, K. Y., Holt, J. T., Sporn, M. B., & Roberts, A. B.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1989-11
Volume
264
Issue
32
Pages
19373-19378
ISSN
0021-9258 (ISSN-L)
OpenAlex
W1570035884
Cited by
183
References
1
FWCI
3.47
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Activation of the second promoter of the transforming growth factor-β1 gene by transforming growth factor-β1 and phorbol ester occurs through the same target sequences. https://app.cochat.ai/papers/10.1016/s0021-9258(19)47311-0
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Kim, S. J., Denhez, F., Kim, K. Y., Holt, J. T., Sporn, M. B., & Roberts, A. B. (1989). Activation of the second promoter of the transforming growth factor-β1 gene by transforming growth factor-β1 and phorbol ester occurs through the same target sequences. Journal of Biological Chemistry. https://doi.org/10.1016/s0021-9258(19)47311-0

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