The role of the chaperones BAG3 and HSPB5 during cancer cachexia

Summary

In our projects, we aim to establish the role of the heat shock protein 70 (Hsp70) machines in protein quality control and failure thereof in case components of it are mutated (in so-called chaperonopathies). We have mainly concentrated on regulators of the Hsp70 that, when mutated, cause (cardio)myopathies, i.e., DNAJB6, HSPB5, and BAG3. Inversely, we explore how key components of these machines can be stimulated such that proteins causing other protein aggregation diseases are prevented from forming toxic aggregates. Again, these include the same 3 Hsp70 regulators (DNAJB6, HSPB5, and BAG3), but they act by different mechanisms and on different disease-related proteins. We are further screening the human chaperone for suppressor of aggregation diseases, also specifically in the context of acting in conjunction with the autophagy machinery. Finally, we have ongoing drug screenings programs for pharmacological activators of chaperones, in particular DNAJB6.

Details

Project number

040.11.732

Main applicant

Prof. dr. H.H. Kampinga

Affiliated with

Rijksuniversiteit Groningen, Universitair Medisch Centrum Groningen, Biomedical Sciences of Cells & Systems (BSCS)

Duration

01/10/2019 to 01/03/2020