Ubiquitination, the process of attaching chains of ubiquitin, a small and conserved protein, marks defective or short-lived proteins for destruction. These marked proteins are swiftly broken down by the proteasome, a macromolecular, ATP-dependent, proteolytic system situated in the cytosol. One example of this degradation process occurs when the CFTR protein misfolds. Consequently, its proteasomal degradation takes place. Additionally, if protein folding is hindered, unfolded proteins accumulate in the RER, causing stress. This stress triggers the unfolded protein response, which leads to an increase in chaperone expression, decreased global translation due to eIF-2 phosphorylation, and the transfer of unfolded proteins to the cytosol. In the cytosol, these unfolded proteins undergo ubiquitination and are subsequently degraded in the proteasome through a process known as ER-associated degradation.
Proteins that are defective (for example, misfolded) or destined for rapid turnover are often marked for destruction by ubiquitination, the covalent attachment of chains of a small, highly conserved protein called ubiquitin (see Fig. 19.3 on p. 247). Proteins marked in this way are rapidly degraded by the proteasome, which is a macromolecular, ATP-dependent, proteolytic system located in the cytosol. For example, misfolding of the CFTR protein (see p. 450) results in its proteasomal degradation. [Note: If folding is impeded, unfolded proteins accumulate in the RER causing stress that triggers the unfolded protein response, in which the expression of chaperones is increased; global translation is decreased by eIF-2 phosphorylation; and the unfolded proteins are sent to the cytosol, ubiquitinated, and degraded in the proteasome by a process called ER-associated degradation.]
VII. CHAPTER SUMMARY