The ubiquitin-dependent proteolytic pathway: specificity of recognition of the proteolytic substrates.
Degradation of intracellular proteins via the ubiquitin system involves several steps. Initially, ubiquitin is covalently linked to the protein substrate in an ATP-dependent reaction. Following ubiquitin conjugation, the protein is selectively degraded with the release of free and reutilizable ubiquitin. Ubiquitin modification of a variety of protein targets within the cell appears to be important in a number of basic cellular functions. For example, modification of core nucleosomal histones may regulate gene expression at the level of chromatin structure. Ubiquitin attachment to cell surface proteins can play a role in the processes of cell-cell interaction and adhesion. Conjugation of ubiquitin to other, yet to be identified protein(s), is probably involved in the progression of cells from one stage to another in the cell cycle. Despite the considerable progress that has been made in elucidating the mode of action and roles of the ubiquitin pathway major problems remain unsolved. One problem of central importance is the issue of what determines the specificity of the ubiquitin ligation system for commitment of certain proteins to degradation. While a free alpha-amino group is one structural feature of the substrate recognized by the ligation system, it is certainly not the only one, and possibly not the predominant recognition marker. The scope of this review is to discuss recent developments in our understanding of the specificity and selection of substrates for conjugation and subsequent degradation via the ubiquitin system.
Ciechanover
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Department of Biochemistry, Rappaport Institute for Research in Medical Sciences, Haifa, Israel.
Schwartz
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D000818:Animals; D006801:Humans; D008025:Ligases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D012343:RNA, Transfer / Q000502:physiology; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000502:physiology*
D011506:Proteins; D014452:Ubiquitins; D012343:RNA, Transfer; D044767:Ubiquitin-Protein Ligases; D008025:Ligases