Heterogeneous nuclear ribonucleoprotein K inhibits heat shock-induced transcriptional activity of heat shock factor 1 [DNA and Chromosomes]

When cells are exposed to heat shock and various other stresses, heat shock factor 1 (HSF1) is activated and the heat shock response (HSR) is elicited. To better understand the molecular regulation of the HSR, we used 2D-PAGE based proteome analysis to screen for heat shock-induced posttranslationally modified cellular proteins. Our analysis revealed that two protein spots typically present on 2D-PAGE gels and containing heterogeneous nuclear ribonucleoprotein K (hnRNP K) with trioxidized Cys132 disappeared after the heat shock treatment and reappeared during recovery, but the total amount of hnRNP K protein remained unchanged. We next tested if hnRNP K plays a role in HSR by regulating HSF1 and found that hnRNP K inhibits HSF1 activity, resulting in reduced expression of hsp70 and hsp27 mRNAs. hnRNP K also reduced binding affinity of HSF1 to the heat shock element (HSE) by directly interacting with HSF1, but did not affect HSF1 phosphorylation-dependent activation or nuclear localization. hnRNP K lost its ability to induce these effects when its Cys132 was substituted with Ser, Asp, or Glu. These findings suggest that hnRNP K inhibits transcriptional activity of HSF1 by inhibiting its binding to HSE and that the oxidation status of Cys132 in hnRNP K is critical for this inhibition.

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