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

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 DDetection 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