Protein intracellular turnover

Ward CL, Kopito RR (1994) Intracellular turnover of cystic fibrosis transmembrane conductance regulator Ineffident processing and rapid degradation of wild-type and mutant proteins.) Biol Chem 269 25710-25718 Ward CL, Omura S, Kopito RR (1995) Degradation of CFTR by the ubiquitin-proteasome pathway. Cell 83 121-127... 

Intracellular Turnover. There are many proteases involved in the turnover of proteins at the intracellular level, all of which have rather restricted specificity. These enzymes, while also present in the cytoplasm, are highly concentrated in the lysosomes. They generally are referred to as cathepsins and include both endo- and exosplitting hydrolases. 

Table VIII. Rates of Intracellular Turnover of Some Selected Proteins ...

Table IX. Factors Affecting Intracellular Turnover of Proteins ...

Figure 5.7 Effect of knockdown of RARa on intracellular turnover of long-lived proteins.

Bayot, A. Basse, N. Lee, I. Gareil, M. Pirotte, B. Bulteau, A. L. Friguet, B. Reboud-Ravaux, M. Towards the control of intracellular protein turnover mitochondrial Lon protease inhibitors versus proteasome inhibitors. Biochimie 2008, 90, 260-269. 

During the last ten years, it has become apparent that calcium-dependent papain-like peptidases called calpains (EC 3.4.22.17) represent an important intracellular nonlysosomal enzyme system [35][36], These enzymes show limited proteolytic activity at neutral pH and are present in virtually every eukaryotic cell type. They have been found to function in specific proteolytic events that alter intracellular metabolism and structure, rather than in general turnover of intracellular proteins. Calpains are composed of two nonidentical subunits, each of which contains functional calcium-binding sites. Two types of calpains, i.e., /i-calpain and m-calpain (formerly calpain I and calpain II, respectively), have been identified that differ in their Ca2+ requirement for activation. The activity of calpains is regulated by intracellular Ca2+ levels. At elevated cytoplasmic calcium concentrations, the precursor procal-pain associates with the inner surface of the cell membrane. This interaction seems to trigger autoproteolysis of procalpain, and active calpain is released into the cytoplasm [37]. 

While ionophore-stimulated 5-LO product release from neutrophils is often used as an indication of 5-LO inhibition, one must interpret these results cautiously. For example, halothane, an inhalation anaesthetic which may cause membrane perturbation [26], and colchicine, a microtubule disrupter [27], both were active, but presumably not because of 5-LO inhibition. A23187 is assumed to stimulate 5-LO by raising the intracellular calcium level, but this agent causes many other effects which may or may not be related to 5-LO activation, including changes in membrane potential, protein phosphorylation, phospholipid turnover, cyclic nucleotide levels, and DNA and protein synthesis [28]. Also, the effects of some putative 5-LO inhibitors on product release from neutrophils has been shown to vary with the stimulant used [29]. 

Poole, B., Ohkuma, S., and Warburton, M. (1978). Some aspects of the intracellular breakdown of exogenous and endogenous proteins. In Segal H.L. and Doyle D.J., eds. Protein Turnover and Lysosome Function. Academic Press, New York, NY USA. pp. 43-58. 

The major current working hypothesis for lithium s therapeutic mechanism of action supposes that its effects on phosphoinositol turnover, leading to an early relative reduction of myoinositol in human brain, are part of an initiating cascade of intracellular changes. Effects on specific isoforms of protein kinase C may be most relevant. Alterations of protein kinase C-mediated signaling alter gene expression and the production of proteins implicated in... 

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