# UBC
## Overview
The UBC gene, short for ubiquitin C, is a crucial component of the cellular machinery responsible for protein degradation and regulation through the ubiquitin-proteasome system. This gene encodes the ubiquitin protein, which plays a pivotal role in tagging defective or surplus proteins for degradation, thereby maintaining protein homeostasis essential for cell survival and function. Ubiquitin itself is not an enzyme or receptor but a small regulatory protein that becomes covalently attached to target proteins, marking them for various fates including degradation, cellular location changes, or modulation of activity. The ubiquitin encoded by UBC is vital not only for protein degradation but also for other cellular processes such as DNA repair, cell cycle control, and response to stress, making it a key player in maintaining cellular integrity and response to environmental cues (Bianchi2015Dynamic; Howard2007Ubiquitin).
## Function
The UBC gene, also known as ubiquitin C, encodes a polyubiquitin precursor that is crucial for various cellular processes through the ubiquitin-proteasome pathway. This pathway is essential for protein degradation, where ubiquitin, a small regulatory protein encoded by UBC, is attached to substrates. These ubiquitinated proteins are then targeted for degradation by the proteasome, a process vital for maintaining protein homeostasis within cells (Bianchi2015Dynamic; Bianchi2009A).
Ubiquitin is also involved in other cellular functions such as cell cycle regulation, DNA repair, transcriptional regulation, signal transduction, endocytosis, and apoptosis. The dynamic regulation of ubiquitin levels is maintained through its recycling by deubiquitinating enzymes and de novo transcription, ensuring that cells can respond to various physiological and stress conditions effectively (Bianchi2009A; Ryu2007The).
Furthermore, the UBC gene is transcriptionally upregulated in response to stress, highlighting its role in cellular stress responses. This upregulation ensures an adequate supply of ubiquitin necessary for handling increased protein damage under stress conditions, thereby aiding in the maintenance of protein quality control (Bianchi2019A; Crinelli2015Molecular).
## Clinical Significance
Mutations or alterations in the expression of the UBC gene, which encodes ubiquitin C, have significant implications for cellular function and can lead to various diseases or conditions. The disruption of the UBC gene in experimental models, such as mice, results in embryonic lethality, underscoring its essential role in development and cellular homeostasis (Kimura2010Regulatory). In humans, similar mutations or dysregulation could potentially result in severe developmental abnormalities or early embryonic death.
Alterations in UBC expression levels are also linked to various pathological conditions. For instance, insufficient ubiquitin levels due to UBC dysfunction can impair the ubiquitin-proteasome pathway, leading to the accumulation of misfolded or damaged proteins. This accumulation is a common feature in neurodegenerative diseases such as Parkinson's and Alzheimer's (Bianchi2018Induction). Additionally, changes in UBC expression have been implicated in cancer, where either upregulation or downregulation of this gene affects cell cycle control and can contribute to tumor progression or suppression (Bianchi2015Dynamic).
Overall, the proper regulation of the UBC gene is crucial for maintaining protein homeostasis and preventing cellular dysfunctions that could lead to disease. Disruptions in its function or expression levels are therefore of clinical significance, highlighting the need for further research into its mechanisms and potential therapeutic targets.
## Interactions
The human gene UBC (ubiquitin C) encodes a protein that is integral to the ubiquitination pathway, which is crucial for protein turnover and cellular regulation. UBC interacts with various proteins, including E1 enzymes, E2 enzymes, and substrates in the ubiquitin-proteasome system. These interactions facilitate the transfer and attachment of ubiquitin to target proteins, regulating their life cycles and various cellular processes such as cell cycle, DNA repair, and response to stress.
Specifically, UBC is involved in the formation of polyubiquitin chains, which are essential for tagging proteins for degradation. This process does not lead to protein degradation by the proteasome but rather modifies substrate proteins for other non-proteolytic processes (Scheper2010Protein-Protein). UBC also participates in the aggregation of polyglutamine proteins, a process relevant in neurodegenerative diseases like Huntington's and Parkinson's disease. RNA interference studies have shown that knockdown of UBC affects the size and number of these protein aggregates, indicating its role in the ubiquitination of aggregate proteins (Howard2007Ubiquitin). Additionally, UBC interacts with UBAITs (Ubiquitin-Activated Interaction Traps), which are tools designed to capture transient protein-protein interactions using the ubiquitin system (O’Connor2018Ubiquitin-Activated). These interactions highlight the diverse roles of UBC in cellular signaling and stress response mechanisms.
## References
[1. (Bianchi2015Dynamic) Marzia Bianchi, Elisa Giacomini, Rita Crinelli, Lucia Radici, Elisa Carloni, and Mauro Magnani. Dynamic transcription of ubiquitin genes under basal and stressful conditions and new insights into the multiple ubc transcript variants. Gene, 573(1):100–109, November 2015. URL: http://dx.doi.org/10.1016/j.gene.2015.07.030, doi:10.1016/j.gene.2015.07.030. (44 citations) 10.1016/j.gene.2015.07.030](https://doi.org/10.1016/j.gene.2015.07.030)
[2. (Ryu2007The) Kwon-Yul Ryu, René Maehr, Catherine A Gilchrist, Michael A Long, Donna M Bouley, Britta Mueller, Hidde L Ploegh, and Ron R Kopito. The mouse polyubiquitin gene ubc is essential for fetal liver development, cell-cycle progression and stress tolerance. The EMBO Journal, 26(11):2693–2706, May 2007. URL: http://dx.doi.org/10.1038/sj.emboj.7601722, doi:10.1038/sj.emboj.7601722. (190 citations) 10.1038/sj.emboj.7601722](https://doi.org/10.1038/sj.emboj.7601722)
[3. (Crinelli2015Molecular) Rita Crinelli, Marzia Bianchi, Lucia Radici, Elisa Carloni, Elisa Giacomini, and Mauro Magnani. Molecular dissection of the human ubiquitin c promoter reveals heat shock element architectures with activating and repressive functions. PLOS ONE, 10(8):e0136882, August 2015. URL: http://dx.doi.org/10.1371/journal.pone.0136882, doi:10.1371/journal.pone.0136882. (26 citations) 10.1371/journal.pone.0136882](https://doi.org/10.1371/journal.pone.0136882)
[4. (Kimura2010Regulatory) Y. Kimura and K. Tanaka. Regulatory mechanisms involved in the control of ubiquitin homeostasis. Journal of Biochemistry, 147(6):793–798, April 2010. URL: http://dx.doi.org/10.1093/jb/mvq044, doi:10.1093/jb/mvq044. (150 citations) 10.1093/jb/mvq044](https://doi.org/10.1093/jb/mvq044)
[5. (Scheper2010Protein-Protein) Johanna Scheper, Marta Guerra-Rebollo, Glòria Sanclimens, Alejandra Moure, Isabel Masip, Domingo González-Ruiz, Nuria Rubio, Bernat Crosas, Óscar Meca-Cortés, Noureddine Loukili, Vanessa Plans, Antonio Morreale, Jerónimo Blanco, Angel R. Ortiz, Àngel Messeguer, and Timothy M. Thomson. Protein-protein interaction antagonists as novel inhibitors of non-canonical polyubiquitylation. PLoS ONE, 5(6):e11403, June 2010. URL: http://dx.doi.org/10.1371/journal.pone.0011403, doi:10.1371/journal.pone.0011403. (35 citations) 10.1371/journal.pone.0011403](https://doi.org/10.1371/journal.pone.0011403)
[6. (Howard2007Ubiquitin) Rebecca A Howard, Pratima Sharma, Connie Hajjar, Kim A Caldwell, Guy A Caldwell, Rusla du Breuil, Rhonda Moore, and Lynn Boyd. Ubiquitin conjugating enzymes participate in polyglutamine protein aggregation. BMC Cell Biology, July 2007. URL: http://dx.doi.org/10.1186/1471-2121-8-32, doi:10.1186/1471-2121-8-32. (30 citations) 10.1186/1471-2121-8-32](https://doi.org/10.1186/1471-2121-8-32)
[7. (Bianchi2018Induction) Marzia Bianchi, Rita Crinelli, Vanessa Arbore, and Mauro Magnani. Induction of ubiquitin c (ubc) gene transcription is mediated by hsf1: role of proteotoxic and oxidative stress. FEBS Open Bio, 8(9):1471–1485, July 2018. URL: http://dx.doi.org/10.1002/2211-5463.12484, doi:10.1002/2211-5463.12484. (37 citations) 10.1002/2211-5463.12484](https://doi.org/10.1002/2211-5463.12484)
[8. (Bianchi2019A) Marzia Bianchi, Rita Crinelli, Elisa Giacomini, Elisa Carloni, Lucia Radici, Emanuele-Salvatore Scarpa, Filippo Tasini, and Mauro Magnani. A negative feedback mechanism links ubc gene expression to ubiquitin levels by affecting rna splicing rather than transcription. Scientific Reports, December 2019. URL: http://dx.doi.org/10.1038/s41598-019-54973-7, doi:10.1038/s41598-019-54973-7. (13 citations) 10.1038/s41598-019-54973-7](https://doi.org/10.1038/s41598-019-54973-7)
[9. (O’Connor2018Ubiquitin-Activated) Hazel F. O’Connor, Caleb D. Swaim, Larissa A. Canadeo, and Jon M. Huibregtse. Ubiquitin-Activated Interaction Traps (UBAITs): Tools for Capturing Protein-Protein Interactions, pages 85–100. Springer New York, 2018. URL: http://dx.doi.org/10.1007/978-1-4939-8706-1_7, doi:10.1007/978-1-4939-8706-1_7. (13 citations) 10.1007/978-1-4939-8706-1_7](https://doi.org/10.1007/978-1-4939-8706-1_7)
[10. (Bianchi2009A) Marzia Bianchi, Rita Crinelli, Elisa Giacomini, Elisa Carloni, and Mauro Magnani. A potent enhancer element in the 5′-utr intron is crucial for transcriptional regulation of the human ubiquitin c gene. Gene, 448(1):88–101, December 2009. URL: http://dx.doi.org/10.1016/j.gene.2009.08.013, doi:10.1016/j.gene.2009.08.013. (89 citations) 10.1016/j.gene.2009.08.013](https://doi.org/10.1016/j.gene.2009.08.013)