26S proteasome regulatory subunit 10 mRNA (PSMC6 mRNA) (PSMC6 mRNA)

PSMC6 mRNA encodes the 26S proteasome regulatory subunit 10, which is an essential ATPase component of the 19S regulatory particle within the 26S proteasome complex (UniProt P62195). This subunit plays a pivotal role in the ATP-dependent unfolding and translocation of ubiquitinated proteins into the 20S proteolytic core for degradation (PubMed: 22121020). In multiple myeloma, malignant plasma cells exhibit a high dependency on the proteasome to maintain protein homeostasis due to excessive immunoglobulin production (PubMed: 33113554). Targeting PSMC6 mRNA with antisense oligonucleotides, such as ION251, induces RNase H-mediated degradation of the transcript, leading to a reduction in PSMC6 protein levels and subsequent proteasome dysfunction (Ionis Pharmaceuticals, 2021). This mechanism triggers severe proteotoxic stress and apoptosis specifically in myeloma cells, offering a novel strategy to treat patients who are refractory to standard proteasome inhibitors like bortezomib (PubMed: 34914755). Clinical development of PSMC6-targeted therapies focuses on patients with relapsed or refractory multiple myeloma who have exhausted standard treatment options.

Other names

Proteasome 26S subunit ATPase 6 mRNAMSS1 mRNAP44 mRNAS10 mRNARPT5 mRNA26S protease regulatory subunit 10 mRNA

Antisense oligonucleotide-mediated degradation of PSMC6 mRNA via RNase H1, leading to reduced levels of the PSMC6 protein and subsequent proteasome dysfunction in cancer cells (PubMed: 33113554).