Extracellular roles for the molecular chaperone, hsp90.
Heat shock proteins (hsps) are versatile molecular chaperones that are responsible for many cellular functions including proper folding, oligomeric assembly, activation, and transport of proteins. Most of the known roles for hsps involve intracellular proteins and processes. Mounting evidence suggests that hsps are present and function in the extracellular space. Hsp90alpha was recently found on the surface and in conditioned media of HT-1080 fibrosarcoma cells. Here it acts as a molecular chaperone that assists in the activation of matrix metalloproteinase-2 (MMP2), leading to increased tumor invasiveness. Few other extracellular substrates of hsp90 have been identified, but several independent observations of extracellular hsp90 suggest that this protein may be important for both normal physiology and disease states. Hsp90 typically works in a complex of associated proteins, and some of these proteins have also been observed extracellularly. Here we show that some of these components, including hsp90 organizing protein (hop) and p23, are also found in HT-1080 conditioned media supporting the notion that hsp90 complexes function in invasiveness. These findings suggest a wide-ranging phenomenon of extracellular molecular chaperoning that could have implications for biological processes and disease.
Department of Physiology, Tufts University School of Medicine, Boston, Massacusetts, USA.
Brenda K
BK
Eustace
Daniel G
DG
Jay
D000818:Animals; D005109:Extracellular Matrix / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D019746:Intramolecular Oxidoreductases; D046911:Macromolecular Substances / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D010750:Phosphoproteins / Q000378:metabolism; D000071876:Prostaglandin-E Synthases
D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D046911:Macromolecular Substances; D018832:Molecular Chaperones; D010750:Phosphoproteins; C489791:Stip1 protein, mouse; D020778:Matrix Metalloproteinase 2; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases