Promotion of heat shock factor Hsf1 degradation via adaptor protein filamin A-interacting protein 1-like (FILIP-1L)

Yanzhong Hu, Nahid F. Mivechi

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27 Scopus citations


Heat 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 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 the Hsf1 protein because FILIP-1L promotes Hsf1 ubiquitination and degradation through the ubiquitin-proteasome system, leading to a reduction in Hsf1-mediated transcription. FILIP-1L, Hsf1, and the ubiquitin-binding domain of HhR23A, a receptor that transports polyubiquitinated proteins to the 19 S 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 ubiquitin-proteasome system.

Original languageEnglish (US)
Pages (from-to)31397-31408
Number of pages12
JournalJournal of Biological Chemistry
Issue number36
StatePublished - Sep 9 2011

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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