tailieunhanh - Báo cáo Y học: Transactivation domains are not functionally conserved between vertebrate and invertebrate serum response factors

The transcription factor serum response factor (SRF) regulates expression of growth factor-dependent genes and muscle-specific genes in vertebrates. Homologous factors regulate differentiation of some ectodermic tissues in invertebrates. To explore the molecular basis of these different physiological functions, the functionality of human, Drosophila melanogaster and Artemia franciscana SRFs in mammalian cells has been compared in this article. D. melanogaster and, to a lesser extend, A. franciscana SRF co-expression represses the activity of strong SRF-dependent promoters, such as those of the mouse c-fos and A. . | Eur. J. Biochem. 269 3669-3677 2002 FEBS 2002 doi Transactivation domains are not functionally conserved between vertebrate and invertebrate serum response factors Sonia Avila Marie-Carmen Casero Rocio Fernandez-Canton and Leandro Sastre Insitituto de Investigaciones Biomedicas CSIC UAM C Arturo Duperier Madrid Spain The transcription factor serum response factor SRF regulates expression of growth factor-dependent genes and muscle-specific genes in vertebrates. Homologous factors regulate differentiation of some ectodermic tissues in invertebrates. To explore the molecular basis of these different physiological functions the functionality of human Drosophila melanogaster and Artemia franciscana SRFs in mammalian cells has been compared in this article. D. melanogaster and to a lesser extend A. franciscana SRF co-expression represses the activity of strong SRF-depen-dent promoters such as those of the mouse c-fos and A. franciscana actin 403 genes. Domain-exchange experiments showed that these results can be explained by the absence of a transactivation domain functional in mammalian cells in D. melanogaster and A. franciscana SRFs. Both invertebrate SRFs can dimerize with endogenous mouse SRF through the conserved DNA-binding and dimerization domain. Co-expression of human and A. franciscana SRFs activate expression of weaker SRF-dependent promoters such as those of the human cardiac a-actin gene or an A. franciscana actin 403 promoter where the SRF-binding site has been mutated. Mapping of A. franciscana SRF domains involved in transcriptional activation has shown that the conserved DNA-binding and dimerization domain is neccessary but not sufficient for promoter activation in mammalian cells. Keywords SRF Artemia Drosophila transcription evolution. The serum response factor SRF is a transcription factor initially isolated as responsible for activation of several immediate early genes such as c-fos in the response of quiescent .

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