Metformin Induces Resistance of Cancer Cells to the Proteasome Inhibitor Bortezomib.

The anti-diabetic drug metformin is currently tested for the treatment of hematological and solid cancers. Proteasome inhibitors, e.g.

In-gel proteasome assay to determine the activity, amount, and composition of proteasome complexes from mammalian cells or tissues.

This protocol describes an easy and reliable in-gel proteasome assay to quantify the activity and composition of different proteasome complexes in cells and tissues. The assay works well with limited amounts of total cell protein lysates. Although this assay is optimized specifically for the proteasome chymotrypsin-like activity, it can be expanded to other proteasome activities as well.

Mitochondrial Regulation of the 26S Proteasome.

The proteasome is the main proteolytic system for targeted protein degradation in the cell and is fine-tuned according to cellular needs. Here, we demonstrate that mitochondrial dysfunction and concomitant metabolic reprogramming of the tricarboxylic acid (TCA) cycle reduce the assembly and activity of the 26S proteasome. Both mitochondrial mutations in respiratory complex I and treatment with the anti-diabetic drug metformin impair 26S proteasome activity.

Exploring the proteasome system: A novel concept of proteasome inhibition and regulation.

The proteasome is a well-identified therapeutic target for cancer treatment. It acts as the main protein degradation system in the cell and degrades key mediators of cell growth, survival and function. The term "proteasome" embraces a whole family of distinct complexes, which share a common proteolytic core, the 20S proteasome, but differ by their attached proteasome activators.

Proteasome activator PA200 regulates myofibroblast differentiation.

The proteasome is essential for the selective degradation of most cellular proteins and is fine-tuned according to cellular needs. Proteasome activators serve as building blocks to adjust protein turnover in cell growth and differentiation. Understanding the cellular function of proteasome activation in more detail offers a new strategy for therapeutic targeting of proteasomal protein breakdown in disease.