Degron
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A degron is a portion of a protein that is important in regulation of protein degradation rates. Known degrons include short amino acid sequences,[2] structural motifs[1] and exposed amino acids (often lysine[3] or arginine[4]) located anywhere in the protein. In fact, some proteins can even contain multiple degrons.[1][5] Degrons are present in a variety of organisms, from the N-degrons (see N-end Rule) first characterized in yeast[6] to the PEST sequence of mouse ornithine decarboxylase.[7] Degrons have been identified in prokaryotes[8] as well as eukaryotes. While there are many types of different degrons, and a high degree of variability even within these groups, degrons are all similar for their involvement in regulating the rate of a protein's degradation.[9][10][11] Much like protein degradation (see proteolysis) mechanisms are categorized by their dependence or lack thereof on ubiquitin, a small protein involved in proteasomal protein degradation,[12][13][14] degrons may also be referred to as either "ubiquitin-dependent"[9] or "ubiquitin-independent".[10][11]
Ubiquitin-dependent degrons are so named because they are implicated in the polyubiquitination process for targeting a protein to the proteasome.[15][16] In some cases, the degron itself serves as the site for polyubiquitination as is seen in TAZ and β-catenin proteins.[17] Because the exact mechanism by which a degron is involved in a protein's polyubiqutination is not always known, degrons are classified as ubiquitin-dependent if their removal from the protein leads to less ubiquitination or if their addition to another protein leads to more ubiquitination.[18][19]
In contrast, ubiquitin-independent degrons are not necessary for the polyubiquitination of their protein. For example, the degron on IκBα, a protein involved in the regulation of the immune system, was not shown to be involved in ubiquitination since its addition to green fluorescent protein (GFP) did not increase ubiquitination.[1] However, a degron can only hint at the mechanism by which a protein is degraded[20] and so identifying and classifying a degron is only the first step in understanding the degradation process for its protein.
