| First Author | Taipale M | Year | 2014 |
| Journal | Cell | Volume | 158 |
| Issue | 2 | Pages | 434-448 |
| PubMed ID | 25036637 | Mgi Jnum | J:213961 |
| Mgi Id | MGI:5586943 | Doi | 10.1016/j.cell.2014.05.039 |
| Citation | Taipale M, et al. (2014) A quantitative chaperone interaction network reveals the architecture of cellular protein homeostasis pathways. Cell 158(2):434-48 |
| abstractText | Chaperones are abundant cellular proteins that promote the folding and function of their substrate proteins (clients). In vivo, chaperones also associate with a large and diverse set of cofactors (cochaperones) that regulate their specificity and function. However, how these cochaperones regulate protein folding and whether they have chaperone-independent biological functions is largely unknown. We combined mass spectrometry and quantitative high-throughput LUMIER assays to systematically characterize the chaperone-cochaperone-client interaction network in human cells. We uncover hundreds of chaperone clients, delineate their participation in specific cochaperone complexes, and establish a surprisingly distinct network of protein-protein interactions for cochaperones. As a salient example of the power of such analysis, we establish that NUDC family cochaperones specifically associate with structurally related but evolutionarily distinct beta-propeller folds. We provide a framework for deciphering the proteostasis network and its regulation in development and disease and expand the use of chaperones as sensors for drug-target engagement. |
