title: Peptide aptamers: tools to negatively or positively modulate HSPB1(27) function.
abstract: Human HSP27 (HSPB1) is a molecular chaperone sensor which, through dynamic changes in its phosphorylation and oligomerization, allows cells to adapt to changes in their physiology and/or mount a protective response to injuries. In pathological conditions, the high level of HSPB1 expression can either be beneficial, such as in diseases characterized by cellular degenerations, or be malignant in cancer cells where it promotes tumourigenesis, metastasis and anti-cancer drug resistance. Structural changes allow HSPB1 to interact with specific client protein partners in order to modulate their folding/activity and/or half-life. Therefore, the search is open for therapeutic compounds aimed at either down- or upregulating HSPB1 activity. In this respect, we have previously described two peptide aptamers (PA11 and PA50) that specifically interact with HSPB1 small oligomers and decrease its anti-apoptotic and tumourigenic activities. A novel analysis of the different HSPB1-interacting aptamers that were isolated earlier revealed that one aptamer (PA23) has the intriguing ability to stimulate the protective activity of HSPB1. We show here that this aptamer abolishes the dominant negative effect induced by the R120G mutant of αB-crystallin (HSPB5) by disrupting its interaction with HSPB1. Hence, developing structure-based interfering strategies could lead to the discovery of HSPB1-based therapeutic drugs.
authors.affiliation: Apoptosis Cancer and Development Laboratory, Lyon Cancer Research Center, Centre Léon Bérard, INSERM U1052-CNRS 5238, University of Lyon, 69008 Lyon, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Gibert
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Simon
authors.forename: Valeriya
authors.initials: V
authors.lastname: Dimitrova
authors.forename: Chantal
authors.initials: C
authors.lastname: Diaz-Latoud
authors.forename: André-Patrick
authors.initials: AP
authors.lastname: Arrigo
mesh_terms: D052158:Aptamers, Peptide / Q000737:chemistry* / Q000378:metabolism*; D005786:Gene Expression Regulation; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006360:Heat-Shock Proteins; D006801:Humans; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation
chemical_list: D052158:Aptamers, Peptide; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones