Extracellular chaperones - protein homeostasis
We are also interested in understanding how secreted protein function is regulated by the extracellular chaperone machinery. The extracellular Hsp90 (eHsp90), like its intracellular counterpart, is responsible for chaperoning client proteins (eg. MMP-2) outside the cell. Regulation of the eHsp90 function by secreted co-chaperones is the focus of our investigation. Our studies have led us to believe that TIMP-2 regulates eHsp90 function which then impacts on MMP-2 activity.
BourbouliaLab
Relevant publications
Votra SD, Alsalih D, Bourboulia D. Methods to Assess the Impact of Hsp90 Chaperone Function on Extracellular Client MMP2 Activity. Methods Mol Biol. 2023;2693:221-232. doi: 10.1007/978-1-0716-3342-7_17. PMID: 37540438.
Backe SJ, Votra SD, Stokes MP, Sebestyén E, Castelli M, Torielli L, Colombo G, Woodford MR, Mollapour M, Bourboulia D. PhosY-secretome profiling combined with kinase-substrate interaction screening defines active c-Src-driven extracellular signaling. Cell Rep. 2023 Jun 27;42(6):112539. doi: 10.1016/j.celrep.2023.112539. Epub 2023 May 25. PubMed PMID: 37243593; NIHMSID:NIHMS1912762.
Baker-Williams AJ, Hashmi F, Budzyński MA, Woodford MR, Gleicher S, HimanenSV, Makedon AM, Friedman D, Cortes S, Namek S, Stetler-Stevenson WG, Bratslavsky G, Bah A, Mollapour M, Sistonen L, Bourboulia D. Co-chaperones TIMP2 and AHA1Competitively Regulate Extracellular HSP90:Client MMP2 Activity and MatrixProteolysis. Cell Rep. 2019 Aug 13;28(7):1894-1906.e6. doi:10.1016/j.celrep.2019.07.045. PubMed PMID: 31412254.
Cortes S, Baker-Williams AJ, Mollapour M, Bourboulia D. Detection and Analysis of Extracellular Hsp90 (eHsp90). Methods Mol Biol. 2018;1709:321-329. doi: 10.1007/978-1-4939-7477-1_23. PMID: 29177669
Remillard T., Bratslavsky G., Jensen-Taubman S., Stetler-Stevenson W.G. and Bourboulia D. Molecular mechanisms of tissue inhibitor of metalloproteinase 2 in the tumor microenvironment. Molecular and Cellular Therapies 2014, 2, 17, PMID: 26056585