Atp

Recycled ubiquitin

Heptameric rings

Catalytically active subunits

19S Regulatory unit

20S proteasome

Small peptide fragments

FIGURE 10.1 Structure and function of the proteasome.

20S proteasome

Small peptide fragments

FIGURE 10.1 Structure and function of the proteasome.

MDM2 ApĀ°ptosis

Acting as a ubiquitin ligase,-'

Senescence p53

Gene expression

Nucleus p53 Degradation

FIGURE 10.2 Negative regulation of p53 by MDM2 and its subsequent degradation by the proteasome.

inhibition prevents completion of the cell cycle and hence the mitotic proliferation of cancer cells.

Proteasome can be classified as an N-terminal nucleophile (Ntn) hydrolase, since the catalytic centers at the p subunits have been identified as N-terminal

I-k B Degradation

NF-kB

Prosurvival pathway

Gene expression

Nucleus

I-k B Degradation

FIGURE 10.3 Proteasome degradation of I-kB stimulates NF-kB-mediated prosurvival pathways in tumor cells.

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