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Myc is an essential negative regulator of platelet-derived growth factor beta receptor expression.
- Oster, S K (author)
- Marhin, W W (author)
- Asker, C (author)
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- Facchini, L M (author)
- Dion, P A (author)
- Post, M (author)
- Sedivy, J M (author)
- Penn, L Z (author)
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- (creator_code:org_t)
- 2000
- 2000
- English.
- In: Molecular and cellular biology. - 0270-7306. ; 20:18, s. 6768-78
- Journal article (peer-reviewed)
Abstract
Subject headings
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- Platelet-derived growth factor BB (PDGF BB) is a potent mitogen for fibroblasts as well as many other cell types. Interaction of PDGF BB with the PDGF beta receptor (PDGF-betaR) activates numerous signaling pathways and leads to a decrease in receptor expression on the cell surface. PDGF-betaR downregulation is effected at two levels, the immediate internalization of ligand-receptor complexes and the reduction in pdgf-betar mRNA expression. Our studies show that pdgf-betar mRNA suppression is regulated by the c-myc proto-oncogene. Both constitutive and inducible ectopic Myc protein can suppress pdgf-betar mRNA and protein. Suppression of pdgf-betar mRNA in response to Myc is specific, since expression of the related receptor pdgf-alphar is not affected. We further show that Myc suppresses pdgf-betar mRNA expression by a mechanism which is distinguishable from Myc autosuppression. Analysis of c-Myc-null fibroblasts demonstrates that Myc is required for the repression of pdgf-betar mRNA expression in quiescent fibroblasts following mitogen stimulation. In addition, it is evident that the Myc-mediated repression of pdgf-betar mRNA levels plays an important role in the regulation of basal pdgf-betar expression in proliferating cells. Thus, our studies suggest an essential role for Myc in a negative-feedback loop regulating the expression of the PDGF-betaR.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- 3T3 Cells
- Animals
- Cell Transformation
- Neoplastic
- Cells
- Cultured
- Down-Regulation
- Kinetics
- Mice
- Mitogens
- pharmacology
- Platelet-Derived Growth Factor
- metabolism
- pharmacology
- Promoter Regions
- Genetic
- Proto-Oncogene Proteins c-myc
- metabolism
- Proto-Oncogene Proteins c-sis
- RNA
- Messenger
- Rats
- Receptor
- Platelet-Derived Growth Factor beta
- genetics
- Repressor Proteins
- metabolism
- Transcription
- Genetic
Publication and Content Type
- ref (subject category)
- art (subject category)
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- Oster, S K
- Marhin, W W
- Asker, C
- Facchini, L M
- Dion, P A
- Funa, Keiko, 194 ...
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- Post, M
- Sedivy, J M
- Penn, L Z
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- MEDICAL AND HEALTH SCIENCES
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- University of Gothenburg
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