Physiological control of smooth muscle-specific gene expression through regulated nuclear translocation of serum response factor

Blanca Camoretti-Mercado, Hong W. Liu, Andrew J. Halayko, Sean M. Forsythe, John W. Kyle, Bei Li, Yiping Fu, John McConville, Paul Kogut, Joaquim E. Vieira, Nina M. Patel, Marc B. Hershenson, Elaine Fuchs, Satrajit Sinha, Joseph M. Miano, Michael S. Parmacek, Janis K. Burkhardt, Julian Solway

Research output: Contribution to journalArticle

102 Scopus citations

Abstract

Prolonged serum deprivation induces a structurally and functionally contractile phenotype in about 1/6 of cultured airway myocytes, which exhibit morphological elongation and accumulate abundant contractile apparatus-associated proteins. We tested the hypothesis that transcriptional activation of genes encoding these proteins accounts for their accumulation during this phenotypic transition by measuring the transcriptional activities of the murine SM22 and human smooth muscle myosin heavy chain promoters during transient transfection in subconfluent, serum fed or 7 day serum-deprived cultured canine tracheal smooth muscle cells. Contrary to our expectation, SM22 and smooth muscle myosin heavy chain promoter activities (but not viral murine sarcoma virus-long terminal repeat promoter activity) were decreased in long term serum-deprived myocytes by at least 8-fold. Because serum response factor (SRF) is a required transcriptional activator of these and other smooth muscle-specific promoters, we evaluated the expression and function of SRF in subconfluent and long term serum-deprived cells. Whole cell SRF mRNA and protein were maintained at high levels in serum-deprived myocytes, but SRF transcription-promoting activity, nuclear SRF binding to consensus CArG sequences, and nuclear SRF protein were reduced. Furthermore, immunocytochemistry revealed extranuclear redistribution of SRF in serum-deprived myocytes; nuclear localization of SRF was restored after serum refeeding. These results uncover a novel mechanism for physiological control of smooth muscle-specific gene expression through extranuclear redistribution of SRF and consequent down-regulation of its transcription-promoting activity.

Original languageEnglish (US)
Pages (from-to)30387-30393
Number of pages7
JournalJournal of Biological Chemistry
Volume275
Issue number39
DOIs
StatePublished - Sep 29 2000

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Camoretti-Mercado, B., Liu, H. W., Halayko, A. J., Forsythe, S. M., Kyle, J. W., Li, B., Fu, Y., McConville, J., Kogut, P., Vieira, J. E., Patel, N. M., Hershenson, M. B., Fuchs, E., Sinha, S., Miano, J. M., Parmacek, M. S., Burkhardt, J. K., & Solway, J. (2000). Physiological control of smooth muscle-specific gene expression through regulated nuclear translocation of serum response factor. Journal of Biological Chemistry, 275(39), 30387-30393. https://doi.org/10.1074/jbc.M000840200