Abstract
The energy dependence of intracellular protein turnover has been recognized for several decades. In the 1950s, Simpson1 and Schwieger et al. 2 showed that respiratory inhibitors decrease the rate of release of amino acids from cells. Therefore, these compounds, which decrease intracellular ATP concentration, inhibit intracellular protein turnover. Since peptide bond hydrolysis is a thermodynamically favorable process, why should protein break down require ATP? And how might ATP hydrolysis be coupled to peptide bond hydrolysis? Our understanding of the mechanistic basis for the ATP requirement has increased substantially in recent years. There are now several known ATP-dependent proteases. One of these is part of the multienzyme pathway that requires the small protein ubiquitin (Ub) as a cofactor. Although Ub-dependent protein breakdown is not the only ATP-dependent protein breakdown in higher eukaryotes,3 it is clear that the Ub-dependent pathway is quantitatively important. Turnover of at least 90% of the short-lived proteins in a mouse mammary carcinoma cell line is Ub dependent.4
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Pickart, C.M. (1988). Ubiquitin Activation and Ligation. In: Rechsteiner, M. (eds) Ubiquitin. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-2049-2_4
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DOI: https://doi.org/10.1007/978-1-4899-2049-2_4
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