Proteasome

The ubiquitin proteasome pathway is the main pathway for intracellular protein degradation and is essential for normal cell function.¹ More than 80% of cellular proteins are degraded through this pathway, including those involved in progression, apoptosis, DNA repair, and protein quality control.² Proteasomal degradation also activates NF-κB signaling, which upregulates anti-apoptotic factors, cell adhesion molecules, cytokines, and growth factors that promote survival of myeloma cells.³

Due to excess production of immunoglobulins and high rates of protein synthesis, myeloma cells are particularly dependent on the proteasome to survive.^1,4 Inhibiting proteasomes in myeloma cells causes accumulation of misfolded and regulatory proteins, which leads to apoptosis.⁴ Proteasome inhibition has also been shown to trigger cell stress and disrupt the tumor microenvironment.³

SEE PROTEASOMES IN ACTION

Learn more about modalities targeting proteasomes:
small molecules.

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NF-kB: nuclear factor kappa-light-chain-enhancer of activated B cells.