Abstract
The ubiquitin proteasome system (UPS) plays a fundamental role in maintaining the correct balance of protein levels inside all living cells. Degradation of proteins by this pathway is essential for most cellular processes including cell signalling, DNA repair, apoptosis and gene transcription. Any disruption to the system is likely to have severe consequences which may lead to disorders including neurodegeneration and cancer. Ubiquitin protein ligases are a group of UPS proteins of particular importance because these proteins determine targeting specificity via recognition of a ‘target’ protein and its subsequent ‘tagging’ with ubiquitin. The 26S proteasome recognises these mutli-ubiquitylated proteins, allowing the correct protein to be degraded at the correct time and place within each cell. Several types of ubiquitin protein ligase have now been identified, however, the largest group by far are those proteins containing a ‘RING’ motif. In this review, examples will be given whereby abnormal protein ubiquitylation due to absence or inefficiency of a RING protein ligase is proposed to be a key regulator of the disease process. Ways in which we may be able to reverse these effects or manipulate these proteins to restore function will be discussed.
Keywords: Ubiquitin protein ligase, disease, small molecule inhibitors
Current Pharmaceutical Design
Title: Ring Finger Ubiquitin Protein Ligases and Their Implication to the Pathogenesis of Human Diseases
Volume: 15 Issue: 31
Author(s): Helen C. Ardley
Affiliation:
Keywords: Ubiquitin protein ligase, disease, small molecule inhibitors
Abstract: The ubiquitin proteasome system (UPS) plays a fundamental role in maintaining the correct balance of protein levels inside all living cells. Degradation of proteins by this pathway is essential for most cellular processes including cell signalling, DNA repair, apoptosis and gene transcription. Any disruption to the system is likely to have severe consequences which may lead to disorders including neurodegeneration and cancer. Ubiquitin protein ligases are a group of UPS proteins of particular importance because these proteins determine targeting specificity via recognition of a ‘target’ protein and its subsequent ‘tagging’ with ubiquitin. The 26S proteasome recognises these mutli-ubiquitylated proteins, allowing the correct protein to be degraded at the correct time and place within each cell. Several types of ubiquitin protein ligase have now been identified, however, the largest group by far are those proteins containing a ‘RING’ motif. In this review, examples will be given whereby abnormal protein ubiquitylation due to absence or inefficiency of a RING protein ligase is proposed to be a key regulator of the disease process. Ways in which we may be able to reverse these effects or manipulate these proteins to restore function will be discussed.
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Cite this article as:
Ardley C. Helen, Ring Finger Ubiquitin Protein Ligases and Their Implication to the Pathogenesis of Human Diseases, Current Pharmaceutical Design 2009; 15 (31) . https://dx.doi.org/10.2174/138161209789271807
DOI https://dx.doi.org/10.2174/138161209789271807 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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