Activation of the Heat Shock Transcription Factor During G1

Abstract

The regulation of the division cycles of eukaryotic cells has been intensively investigated in recent years and appears to involve both changes in gene expression and posttranslational modification of preexisting proteins1–3. Cell-cycle dependent transcription has been shown to be regulated by a number of transcription factors. Most of these factors are associated with the progression of cells from G0 to G1. The nature of the factors involved in cell cycle stage dependent transcription is more obscure although factors involved in the expression of the histone genes have been described4 and the recent discovery of the E2F transcription factor which may regulate events during G1 and S has supplied the link between cell cycle dependent transcription and the cyclin-cdc2 system that drives the cell cycle5–7. The regulation of G1 appears to be highly complex with at least three families of cyclins acting at different stages and with apparently discrete functions in the cell 2, 8. in the present report, we have examined the potential role of members of the heat shock transcription factor (HSF) family in cell cycle-dependent transcription. Cells from higher eukaryotic organisms express 2–3 distinct HSF genes9, 10. The prototypical family member, HSF-1 regulates transcription of genes encoding heat shock proteins (hsp) during stress while the functions of the other family members remain largely unknown9, 11. The rationale for investigating HSF activity during the cell cycle is that the expression of heat shock proteins, the downstream products of HSF activation is observed during the division cycles of many cell types12–14 We observed HSF activation during the early stages of G1 which was associated with the transcription of heat shock genes and the synthesis of heat shock mRNA and proteins. Using antibodies specific for HSF-1 and HSF-2, we identified the species active during G1 as HSF-l. HSF-l activation possessed many of the properties associated with a key point in the cell cycle known as the restriction point including a transient lifetime (3hr) and a marked sensitivity to cycloheximide treatment.