Calreticulin is transcriptionally upregulated by heat shock, calcium and heavy metals

Tho Q. Nguyen, J. Donald Capra, Richard D. Sontheimer

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

Calreticulin is a new human rheumatic disease-associated autoantigen that plays a multifaceted role in cell biology. In earlier studies, this protein was shown to share an intimate relationship with the Ro/SS-A autoantigen complex, although the nature of this association continues to be debated. Since modulation of the Ro/SS-A autoantigen in epidermal keratinocytes has been implicated in the pathogenesis of subacute cutaneous lupus erythematosus and neonatal lupus erythematosus, we have begun to examine the transcriptional regulation of calreticulin. A 504 bp calreticulin promoter fragment was subcloned into a reporter gene plasmid containing firefly luciferase. Calcium ionophore, heat shock, and heavy metals such as zinc and cadmium were consistently found to increase calreticulin transcriptional activities in A431 cells (a human epidermoid squamous carcinoma cell line) under transient transfection conditions. These studies suggest that (a) calreticulin is regulated at the transcriptional level, and (b) calreticulin, like some other LE-related autoantigens, appears to function as a heat shock/stress-response gene.

Original languageEnglish (US)
Pages (from-to)379-386
Number of pages8
JournalMolecular Immunology
Volume33
Issue number4-5
DOIs
StatePublished - 1996

Keywords

  • Heat shock protein
  • calreticulin
  • keratinocyte
  • luciferase
  • transcriptional regulation

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

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