Proteolysis Enzyme regulation

Rechsteiner M Regulation of enzyme levels by proteolysis The role of pest regions. Adv Enzyme Regul 1988 27 135-151. 

The last chapter discussed noncovalent interactions that regulate enzyme activity. The body also uses covalent changes for enzyme regulation. In some cases, the changes are reversible, as in the case of protein phorylation in other cases, the changes are irreversible, as in the use of proteolysis as an activation mechanism. 

The 26S proteasome also degrades non-ubiquitylated proteins [71]. The short-lived enzyme ornithine decarboxylase (ODC) and the cell-cycle regulator p21Cip provide well documented examples of ubiquitin-independent proteolysis by the 26S en-... 

Figure 20.31 The principle of interconversion cycles in regulation of protein activity or changes in protein concentration as exemplified by translation/proteolysis or protein kinase/protein phosphatase. They result in very marked relative changes in regulator concentration or enzyme activity. The significance of the relative changes (or sensitivity in regulation) is discussed in Chapter 3. The principle of regulation by covalent modihcation is also described in Chapter 3. The modifications in cyclin concentration are achieved via translation and proteolysis, which, in effect, is an interconversion cycle. For the enzyme, they are achieved via phosphorylation and dephosphorylation reactions. In both cases, the relative change in concentration/activity by the covalent modification is enormous. This ensures, for example, that a sufficient increase in cyclin can occur so that an inactive cell cycle kinase can be converted to an active cell cycle kinase, or that a cell cycle kinase can be completely inactivated. Appreciation of the common principles in biochemistry helps in the understanding of what otherwise can appear to be complex phenomena.

In vivo participation of E3 enzymes can be assumed generally and it seems likely that proteolysis is controlled primarily by regulating the activity of the E3 s. Although they are thought to be most directly involved in substrate recognition this class of enzymes is least well understood. E3s might be divided into distinct families with regard to sequence class and enzymatic... 

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