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Editorial
. 2013 Sep 15;12(18):2929-30.
doi: 10.4161/cc.26213. Epub 2013 Aug 23.

The weakest link: a new paradigm for stabilizing the integrin-actin connection

Jessica Morgner  1 , Sara A Wickström
Affiliations
Editorial

The weakest link: a new paradigm for stabilizing the integrin-actin connection

Jessica Morgner et al. Cell Cycle. .
No abstract available

Keywords: CHIP; Hsp90; cell adhesion; chaperone; cytoskeleton; extracellular matrix; fibrosis; focal adhesion; integrin; integrin-linked kinase; ubiquitination.

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Figure 1. A model of how stability of ILK is regulated by the Hsp90/CHIP axis. Binding of Hsp90 to the kinase domain (KD) of ILK stabilizes ILK and enables its interaction with parvin. The ILK–parvin complex links integrins to the actin cytoskeleton at focal adhesion sites and facilitates cellular force generation, a prerequisite for migration and matrix remodeling. Incorrect folding of ILK or blocking of Hsp90 activity by 17AAG leads to the recruitment of the chaperone Hsc70 and E3 ligase CHIP to bind ILK. CHIP binds via its UBox domain to the ankyrin-repeat domain (ARD) of ILK, resulting in polyubiquitination of ILK and its subsequent targeting for proteasomal degradation. Pathological deposition of extracellular matrix in fibrosis can be attenuated by inhibiting Hsp90.
See this image and copyright information in PMC

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References

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