The Disordered Amino-Terminus of SIMPL Interacts with Members of The 70-kDa Heat-Shock Protein Family
Document Type
Article
Publication Date
2006
Digital Object Identifier (DOI)
https://doi.org/10.1089/dna.2006.25.704
Abstract
The p65 coactivator SIMPL is a small protein that lacks any conserved domains of known function. To better understand regulation of SIMPL activity, we sought to identify novel SIMPL interacting proteins using mass spectrometry analysis of SIMPL containing complexes. Two members of the 70-kDa heat-shock protein family, Hsp70 and Hsc70, were identified as SIMPL binding proteins. Subsequent immunocomplexing assays confirmed this interaction and demonstrated that the amino-terminus of SIMPL is required for this interaction. Using a combination of amino acid composition analysis, PONDR® VL-XT prediction, charge-hydropathy plots, and cumulative distribution functions, the amino-terminal region of both mouse and human SIMPL proteins was predicted to be intrinsically disordered. These data, taken together, suggest that Hsp70/Hsc70 bind the intrinsically disordered amino-terminal region of SIMPL to stabilize the protein and thereby regulate its activity. Understanding the regulation of SIMPL through its interaction with Hsp70/Hsc70 may serve as a novel means of modulating tumor necrosis factor alpha signaling.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
DNA and Cell Biology, v. 25, issue 12, p. 704-714
Scholar Commons Citation
Breese, Erin Haag; Uversky, Vladimir N.; Georgiadis, Millie M.; and Harrington, Maureen A., "The Disordered Amino-Terminus of SIMPL Interacts with Members of The 70-kDa Heat-Shock Protein Family" (2006). Molecular Medicine Faculty Publications. 771.
https://digitalcommons.usf.edu/mme_facpub/771
