ULTRAVIOLET-LIGHT ATTENUATES HEAT-INDUCIBLE GENE-EXPRESSION

Ultraviolet light (UV) induces a stress response mediated through tran scription factors such as NF-kB and AP-1 yet little is known about its effect on other transactivators of stress gene expression such as hea t shock factor (HSF1). Analysis of UV-treated HeLa cells unexpectedly revealed uncoupling of the heat shock response. UV weakly induced HSF1 into its DNA bound state and markedly attenuated heat-inducible gene expression. HSF1 was further analyzed as a potential target for the un characteristic uncoupling of the thermal stress response by another ty pe of stress. Heat-inducible multimerization and nuclear translocation of HSF1 were found to be intact in UV-treated cells; however, the mon omeric rather than the multimeric form of HSF1 become hyperphosphoryla ted by UV. This effect could be partially abolished by the antioxidant N-acetyl cysteine With partial reconstitution of hs gene expression. The reported role of a MAP kinase blockade of HSF1 transactivating pro perties could not be confirmed by an inhibitor of the MAP kinase pathw ay. Fibroblasts defective in SAP kinase activity also did not exhibit resistance to UV-inducible phosphorylation of HSF1. Two-dimensional ph osphopeptide mapping of HSF1 revealed a single tryptic peptide to be a ffected by UV, but no new pattern of phosphorylation was evident relat ive to tryptic phosphopeptide profile observed in control cells. These data suggest that UV uncoupling of the hs response possibly involves steps in addition to those associated With phosphorylation the monomer ic form of HSF1. (C) 1997 Wiley-Liss, Inc.