Key Concepts Of Section 146

Pathways That Involve Signal-Induced Protein Cleavage

■ The NF-kB transcription factor regulates many genes that permit cells to respond to infection and inflammation.

■ In unstimulated cells, NF-kB is localized to the cytosol, bound to an inhibitor protein, I-kB. In response to extracellular signals, phosphorylation-dependent ubiquitination and degradation of I-kB in proteasomes releases active NF-kB, which translocates to the nucleus (see Figure 14-28).

■ Upon binding to its ligand Delta on the surface of an adjacent cell, the Notch receptor protein undergoes two proteolytic cleavages. The released Notch cytosolic segment then translocates into the nucleus and modulates gene transcription (see Figure 14-29).

■ Presenilin 1, which catalyzes the regulated intramembrane cleavage of Notch, also participates in the cleavage of amyloid precursor protein (APP) into a peptide that forms plaques characteristic of Alzheimer's disease.

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