Hu Y, Mivechi NF

HHeat shock factor Hsf1 is involved in the regulation of a variety of cellular processes including heat shock response, development and differentiation, aging, and tumorigenesis. Hsf1 transcriptional activity is tightly controlled through phosphorylation, sumoylation, and acetylation, and through association with a number of regulatory proteins. However, regulation of Hsf1 protein ...

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stability or turnover remains unknown. We have identified a novel Hsf1-interacting protein, FILIP-1L, that was found to bind to Hsf1 through yeast two-hybrid screening. FILIP-1L encodes multiple isoforms spanning from 711 to 1135 amino acid residues. FILIP-1L contains four coiled-coil and two N-terminal leucine zipper domains. Ectopic expression of FILIP-1L reduces the expression of Hsf1 protein since FILIP-1L promotes Hsf1 ubiquitination and degradation through the ubiquitin-proteasome system (UPS), leading to a reduction in Hsf1-mediated transcription. FILIP-1L, Hsf1, and ubiquitin binding domain (UBA) of HhR23A, a receptor that transports polyubiquitinated proteins to the 19S proteasome subunit targeting them for degradation, are found in a complex. This indicates that FILIP-1L is a potential adaptor that is involved in the Hsf1 degradation pathway. Taken together, our results indicate that FILIP-1L interacts with Hsf1, controlling its stability and thus modulating the heat shock response. These data indicate a novel function for FILIP-1L and a pathway for Hsf1 degradation through the UPS.

Date: Jul. 22, 2011

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