Role of proteasomes in protein degradation and nuclear factor-κ
B activation. (A) After initial synthesis, proteins at the end of their (functional) life-span, or damaged/misfolded proteins, are subject to degradation after conjugating with an ubiquitin (Ub) tag. Recognition by the proteasome initiates protein degradation to smaller peptides, which are further processed by aminopeptidases either to free amino acid for renewed protein synthesis or to trimmed peptides presented by major histocompatibility complex class I molecules. (B) Mechanism of blockade of nuclear factor (NF)-κB activation by the proteasome inhibitor bortezomib. This inhibitory effect prevents the degradation of the natural inhibitor of NF-κB (that is, IκB) along with nuclear translocation of p50/p65 and transcription of pro-inflammatory cytokines. IL, interleukin; TNF, tumor necrosis factor.