Amino acid degradation proteasomes

At least three distinct forms of the IP3-R have been identified, and these share an overall amino acid homology of 60-80%. Type I predominates in the cerebellum and has been most extensively studied. It is the largest of the 3 forms of the receptor and, unlike type II and III receptors, the gene possesses a 120 nucleotide insert. Type II IP3-Rs are found mainly in non-neural tissues, whereas type III receptors occur in both neural and non-neural tissues. In response to chronic activation, IP3-Rs are degraded via the ubiquitin-proteasome pathway [14] (see also Ch. 2). 

It has been reported that the GRR that spans amino acid residues 476-304 in human pl05, is an important structural motif required for the generation of the p50 subunit of NF-kB (10). However, the mechanisms involved in this unique reaction have remained enigmatic. Since degradation of a protein via the ubiquitin pathway involves two steps, conjugation of ubiquitin and proteasomal degradation of the tagged substrate, it was important first to identify the step affected by the GRR. 

Sharipo A, Imreh M, Leonchiks A, Branden C, and Masucci MG (2001) cis-Inhibition of proteasomal degradation by viral repeats impact of length and amino acid composition. FEES Lett. 499 137-142. 

An initially surprising conclusion drawn from the studies of Schoenheimer and Rittenberg was that proteins within cells are in a continuous steady state of synthesis and degradation. The initial biosynthesis, the processing, oxidative and hydrolytic degradative reactions of peptides, and further catabolism of amino acids all combine to form a series of metabolic loops as discussed in Chapter 17 and dealt with further in Chapters 12 and 29. Within cells some proteins are degraded much more rapidly than others, an important aspect of metabolic control. This is accomplished with the aid of the ubiquitin system (Box 10-C) and proteasomes (Box 7-A).107 Proteins secreted into extracellular fluids often undergo more rapid turnover than do those that remain within cells. 

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