Proteasome and nuclear factor kappa-light-chain-enhancer of activated B cells pathway (NF-κB pathway (for the signaling pathway); proteasome is typically not abbreviated in clinical or pharmacological contexts.)

The proteasome is a large, multi-subunit enzyme complex responsible for most intracellular protein degradation, functioning through the ubiquitin-proteasome pathway. By regulating the turnover of key regulatory proteins, it plays a vital role in cellular homeostasis, apoptosis, cell cycle control, and stress responses. The NF-κB pathway is a major transcriptional pathway controlling immune response, inflammation, cell survival, and proliferation. NF-κB proteins are normally sequestered in the cytoplasm by inhibitory IκB proteins; upon activation (often due to tissue damage, infection, or inflammatory cytokines), IκB is phosphorylated and degraded by the proteasome, allowing NF-κB to translocate to the nucleus and induce gene expression. Dysregulation of either the proteasome or NF-κB is implicated in cancers, chronic inflammation, and many autoimmune or infectious diseases. Therapeutic targeting often focuses on inhibiting proteasomal degradation or blocking NF-κB pathway activation to reduce pathological cell survival or inflammation[1][2][4][5][3][7].

Other names

Ubiquitin-proteasome pathway (sometimes for proteasome)Nuclear factor kappa B pathway (for NF-κB pathway)NF-κB signalingUPS-NF-κB axis (rare; indicates regulatory coupling)

Proteasome inhibitors: Block the proteolytic activity of the 26S proteasome, preventing degradation of IκB, leading to retained cytoplasmic NF-κB and reduced transcriptional activation of pro-survival and pro-inflammatory genes. NF-κB pathway inhibitors: Prevent phosphorylation and degradation of inhibitory IκB proteins (directly or indirectly); Block nuclear translocation and DNA binding of NF-κB dimers; Suppress pro-inflammatory gene induction; Modulate upstream signals (cytokines, receptor activation).