title: Promotion of heat shock factor Hsf1 degradation via adaptor protein filamin A-interacting protein 1-like (FILIP-1L).
abstract: 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.
authors.affiliation: Center for Molecular Chaperone/Radiobiology and Cancer Virology, Georgia Health Sciences University, Augusta, Georgia 30912, USA.
authors.forename: Yanzhong
authors.initials: Y
authors.lastname: Hu
authors.forename: Nahid F
authors.initials: NF
authors.lastname: Mivechi
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D003285:Contractile Proteins; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D064448:Filamins; D000076249:Heat Shock Transcription Factors; D018869:Heat-Shock Response; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D003285:Contractile Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C464562:FILIP1 protein, human; D064448:Filamins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D008840:Microfilament Proteins; D014157:Transcription Factors; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex