Stabilization of integrin-linked kinase by the Hsp90-CHIP axis impacts cellular 
force generation, migration and the fibrotic response

Radovanac, K.; Morgner, J.; Schulz, J. N.; Blumbach, K.; Patterson, C.; Geiger, T.; Mann, M.; Krieg, T.; Eckes, B.; Fassler, R.; Wickström, S. A.

doi:10.1038/emboj.2013.90

Item

ITEM ACTIONSEXPORT

Add to Basket

Local TagsRelease HistoryDetailsSummary

Released

Journal Article

Stabilization of integrin-linked kinase by the Hsp90-CHIP axis impacts cellular force generation, migration and the fibrotic response

MPS-Authors

Radovanac, K.
Max Planck Society;

Morgner, J.
Max Planck Society;

Schulz, J. N.
Max Planck Society;

Blumbach, K.
Max Planck Society;

Patterson, C.
Max Planck Society;

Geiger, T.
Max Planck Society;

Mann, M.
Max Planck Society;

Krieg, T.
Max Planck Society;

Eckes, B.
Max Planck Society;

Fassler, R.
Max Planck Society;

Wickström, S. A.
Max Planck Society;

External Resource

http://www.ncbi.nlm.nih.gov/pubmed/23612611
(Any fulltext)

Fulltext (public)

There are no public fulltexts stored in PuRe

Supplementary Material (public)

There is no public supplementary material available

Citation

Radovanac, K., Morgner, J., Schulz, J. N., Blumbach, K., Patterson, C., Geiger, T., et al. (2013). Stabilization of integrin-linked kinase by the Hsp90-CHIP axis impacts cellular force generation, migration and the fibrotic response. EMBO J, 32(10), 1409-24. doi:10.1038/emboj.2013.90.

Cite as: http://hdl.handle.net/11858/00-001M-0000-0028-5994-8

Abstract

Integrin-linked kinase (ILK) is an adaptor protein required to establish and maintain the connection between integrins and the actin cytoskeleton. This linkage is essential for generating force between the extracellular matrix (ECM) and the cell during migration and matrix remodelling. The mechanisms by which ILK stability and turnover are regulated are unknown. Here we report that the E3 ligase CHIP-heat shock protein 90 (Hsp90) axis regulates ILK turnover in fibroblasts. The chaperone Hsp90 stabilizes ILK and facilitates the interaction of ILK with alpha-parvin. When Hsp90 activity is blocked, ILK is ubiquitinated by CHIP and degraded by the proteasome, resulting in impaired fibroblast migration and a dramatic reduction in the fibrotic response to bleomycin in mice. Together, our results uncover how Hsp90 regulates ILK stability and identify a potential therapeutic strategy to alleviate fibrotic diseases.