Protein degradation, regulated

HoppeT. (2008) Lessismore how protein degradation regulates muscle development. Ernst Schering Foundation Symposium Proceedings 1, 67-Ti. 

Mammals, fungi, and higher plants produce a family of proteolytic enzymes known as aspartic proteases. These enzymes are active at acidic (or sometimes neutral) pH, and each possesses two aspartic acid residues at the active site. Aspartic proteases carry out a variety of functions (Table 16.3), including digestion pepsin and ehymosin), lysosomal protein degradation eathepsin D and E), and regulation of blood pressure renin is an aspartic protease involved in the production of an otensin, a hormone that stimulates smooth muscle contraction and reduces excretion of salts and fluid). The aspartic proteases display a variety of substrate specificities, but normally they are most active in the cleavage of peptide bonds between two hydrophobic amino acid residues. The preferred substrates of pepsin, for example, contain aromatic residues on both sides of the peptide bond to be cleaved. 

Cell Cycle Regulation by Ubiqnitin-Mediated Protein Degradation... 

Ubiquitin Many Protein degradation, sorting, regulation... 

The functional proteins in the cell have to be protected in order to prevent premature degradation. Some of the intracellularly active proteolytic enzymes are therefore enclosed in lysosomes (see p. 234). The proteinases that act there are also known as cathepsins. Another carefully regulated system for protein degradation is located in the cytoplasm. This consists of large protein complexes (mass 2 10 Da), the proteasomes. Proteasomes contain a barrel-shaped core consisting of 28 subunits that has a sedimentation coef cient (see p. 200) of 20 S. Proteolytic activity (shown here by the scissors) is localized in the interior of the 20-S core and is therefore protected. The openings in the barrel are sealed by 19-S particles with a complex structure that control access to the core. 

The synthesis and degradation of muscle proteins are regulated by hormones. Cortisol leads to muscle degradation, while testosterone stimulates protein formation. Synthetic anabolics with a testosterone-like effect have repeatedly been used for doping purposes or for intensive muscle-building. 

Cortisol, the most important g/ucocorticoid, is synthesized by the adrenal cortex, it is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose. As a result, the blood glucose level rises (see p. 152). Synthetic glucocorticoids (e.g., dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects. 

In many cases of regulated protein degradation it was shown that ubiquit-ination is positively regulated by phosphorylation. This holds true also for endocytosis. Internalization of the a-factor receptor, for example, was shown to depend on specific serine residues in the cytoplasmic tail. They are found in a 9 amino acid motive, SINNDAKSS, which is essential for endocytosis. Mutant versions of Ste2 in which the three serine residues have been... 

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