Heat and heavy metal stress synergize to mediate transcriptional hyperactivation by metal-responsive transcription factor MTF-1.
J Biol Chem
; 278(34): 31879-83, 2003 Aug 22.
Article
em En
| MEDLINE
| ID: mdl-12805380
ABSTRACT
Mammalian cells react to heavy metal stress by transcribing a number of genes that contain metal-response elements (MREs) in their promoter/enhancer region; this activation is mediated by metal-responsive transcription factor-1 (MTF-1). Well-known target genes of MTF-1 are those encoding metallothioneins, small, cysteine-rich proteins with a high affinity for heavy metals. The response to heat shock, another cell stress, is mediated by heat shock transcription factor 1 (HSF1), which activates a battery of heat shock genes. Little is known about the cross-talk between the different anti-stress systems of the cell. Here we report a synergistic activation of metal-responsive promoters by heavy metal load (zinc or cadmium) and heat shock. An obvious explanation, cooperativity between MTF-1 and HSF1, seems unlikely transfected HSF1 boosts the activity of an Hsp70 promoter but hardly affects an MRE-containing promoter upon exposure to metal and heat shock. A clue to the mechanism is given by our finding that heat shock leads to intracellular accumulation of heavy metals. We propose that the known anti-apoptotic effect of heat shock proteins allows for cell survival despite heavy metal accumulation and, consequently, results in a hyperactivation of the metal response pathway.
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Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Transcrição Gênica
/
Metais Pesados
/
Temperatura Alta
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article