دورية أكاديمية
Requirement for cAMP-response element (CRE) binding protein/CRE modulator transcription factors in thyrotropin-induced proliferation of dog thyroid cells in primary culture.
| العنوان: | Requirement for cAMP-response element (CRE) binding protein/CRE modulator transcription factors in thyrotropin-induced proliferation of dog thyroid cells in primary culture. |
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| المؤلفون: | Uyttersprot N; Interdisciplinary Research Institute, Free University of Brussels, Belgium., Costagliola S, Dumont JE, Miot F |
| المصدر: | European journal of biochemistry [Eur J Biochem] 1999 Jan; Vol. 259 (1-2), pp. 370-8. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Blackwell Science Ltd. on behalf of the Federation of European Biochemical Societies Country of Publication: England NLM ID: 0107600 Publication Model: Print Cited Medium: Print ISSN: 0014-2956 (Print) Linking ISSN: 00142956 NLM ISO Abbreviation: Eur J Biochem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: -2004: Oxford, UK : Blackwell Science Ltd. on behalf of the Federation of European Biochemical Societies Original Publication: Berlin, New York, Springer. |
| مواضيع طبية MeSH: | Cyclic AMP/*metabolism , Cyclic AMP Response Element-Binding Protein/*metabolism , DNA-Binding Proteins/*metabolism , Repressor Proteins/*metabolism , Thyroid Gland/*metabolism , Thyrotropin/*pharmacology, Animals ; Cell Division ; Cells, Cultured ; Cyclic AMP Response Element Modulator ; Dogs ; Fluorescent Antibody Technique, Indirect ; Mitogens ; Phosphorylation ; Signal Transduction ; Thyroid Gland/cytology ; Thyroid Gland/drug effects ; Up-Regulation |
| مستخلص: | In several cell types, mostly of epithelial origin, activation of the cAMP pathway triggers DNA synthesis and cell division. Regulation of gene expression by cAMP involves phosphorylation by pyruvate kinase A and activation of cAMP-response element binding protein (CREB)/CRE modulator (CREM) transcription factors which bind DNA to CRE sites. On the other hand, several CREM isoforms are transcriptional repressors, such as the inducible cAMP early repressor (ICER) transcription factors, which are synthesized from an intronic promoter of the CREM gene. This study investigated the potential role of CREB/CREM transcription factors in the cAMP mitogenic pathway, using an experimental model of epithelial cells in primary culture, i.e. dog thyroid cells stimulated by thyroid-stimulating hormone (TSH). In response to TSH, CREB/CREM transcription factors were phosphorylated on the serine residue of the pyruvate kinase A consensus site. In addition, the synthesis of ICER mRNAs was strongly induced by TSH. This transient upregulation of ICER expression correlated with increased protein levels. It was restricted to the cAMP pathway, as neither epidermal growth factor nor phorbol myristate acetate, which are potent mitogens for dog thyroid cells, induced ICER expression. On the other hand, increased expression of ICER mRNAs was not detected in dog thyroids chronically stimulated by TSH in vivo. The requirement for CREB/CREM transcription factors in the mitogenic effect of TSH was assessed by transfecting expression vectors encoding CREM repressors into dog thyrocytes in order to interfere with CRE-mediated gene transcription. The ectopic expression of ICER Igamma or CREM alpha isoforms inhibited DNA replication in dog thyrocytes stimulated by TSH. This inhibitory effect was dependent on the ability of CREM repressors to form dimers but did not involve their DNA-binding capacity. Together these results show that CREB/CREM transcription factors are tightly regulated, at the transcriptional and post-translational levels, by TSH in dog thyroid cells, and provide clear evidence that their activity is required for the cAMP-dependent proliferation of cells in primary culture. Moreover, the transient induction of ICER transcription factors during mitogenic stimulation by TSH raises questions about the role of these potent repressors of CRE-dependent transcription as timers of cellular proliferation. |
| المشرفين على المادة: | 0 (Cyclic AMP Response Element-Binding Protein) 0 (DNA-Binding Proteins) 0 (Mitogens) 0 (Repressor Proteins) 135844-64-3 (Cyclic AMP Response Element Modulator) 9002-71-5 (Thyrotropin) E0399OZS9N (Cyclic AMP) |
| تواريخ الأحداث: | Date Created: 19990123 Date Completed: 19990305 Latest Revision: 20190620 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1046/j.1432-1327.1999.00049.x |
| PMID: | 9914516 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 0014-2956 |
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| DOI: | 10.1046/j.1432-1327.1999.00049.x |