Transient inhibition of protein synthesis induces the immediate early gene VL30: Alternative mechanism for thapsigargin-induced gene expression

B. E. Magun, K. D. Rodland

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Induction of gene expression in response to calcium ionophores or thapsigargin, which inhibits the calcium-ATPase responsible for sequestering intracellular calcium, has frequently been attributed to direct stimulatory events subsequent to the elevation of intracellular free calcium. VL30 is a murine gene that is transcriptionally induced in response to a large array of mitogenic and transforming stimuli. We have shown previously that an enhancer element within the VL30 promoter region is dependent upon cotreatment with thapsigargin or calcium ionophore for a full-scale induction of gene expression. In this report, we demonstrate that both thapsigargin and calcium ionophores induce a transient inhibition of protein synthesis in Rat-1 cells transfected with a VL30 enhancer-driven reporter construct. Recovery of protein synthesis is facilitated by cotreatment with epidermal growth factor or phorbol esters. Furthermore, treatment with cycloheximide or DTT, which inhibit protein synthesis without altering intracellular calcium levels, can substitute for thapsigargin or ionophores in stimulating VL30 gene expression. These results suggest that the stimulatory effects of thapsigargin and calcium ionophores on VL30 expression may be mediated, at least in part, by the ability of these agents to initiate stress responses associated with the inhibition of protein synthesis.

Original languageEnglish (US)
Pages (from-to)891-897
Number of pages7
JournalCell Growth and Differentiation
Volume6
Issue number7
StatePublished - 1995

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Immediate-Early Genes
Thapsigargin
Calcium Ionophores
Gene Expression
Proteins
Calcium
Calcium-Transporting ATPases
Ionophores
Phorbol Esters
Cycloheximide
Epidermal Growth Factor
Genetic Promoter Regions
Genes

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Transient inhibition of protein synthesis induces the immediate early gene VL30 : Alternative mechanism for thapsigargin-induced gene expression. / Magun, B. E.; Rodland, K. D.

In: Cell Growth and Differentiation, Vol. 6, No. 7, 1995, p. 891-897.

Research output: Contribution to journalArticle

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