Ubiquitin C gene: Structure, function, and transcriptional regulation

DOI: 10.4236/abb.2013.412141   PDF   HTML   XML   6,195 Downloads   9,266 Views   Citations


Ubiquitin C (UbC) is one of the four genes encoding for ubiquitin in the mammalian genome. It has been described as the most responsive gene to cellular treats such as UV irradiation, heat shock, oxidative stress and translational impairment; it was also reported to contribute to maintaining ubiquitin steady state levels under physiological conditions. Despite the bulk of knowledge concerning its function, little is known about the molecular mechanisms modulating UbC expression. Here we review the state of the art of UbC structure, function and transcriptional regulation. Starting from the first evidences which circumscribed the genomic region, pointing out both basic promoter marks (such as transcription start site and TATA-like element), and transcript structure (exonintron boundaries) we go through more detailed molecular studies performed by Marinovic in 2002 and by Bianchi et al. in 2009 and 2013. Herein, the key players orchestrating UbC gene basal activity are underlined.

Share and Cite:

Radici, L. , Bianchi, M. , Crinelli, R. and Magnani, M. (2013) Ubiquitin C gene: Structure, function, and transcriptional regulation. Advances in Bioscience and Biotechnology, 4, 1057-1062. doi: 10.4236/abb.2013.412141.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Goldknopf, I.L., et al. (1975) Isolation and characterization of protein A24, a “histone-like” non-histone chromosomal protein. The Journal of Biological Chemistry, 250, 7182-7187.
[2] Mukhopadhyay, D. and Riezman, H. (2007) Proteasome-independent functions of ubiquitin in endocytosis and signaling. Science, 315, 201-205.
[3] Clague, M.J. and Urbé, S. (2010) Ubiquitin: Same molecule, different degradation pathways. Cell, 143, 682-685.
[4] Pickart, C.M. (2001) Mechanisms underlying ubiquitination. Annual Review of Biochemistry, 70, 503-533.
[5] Shih, S.C., Sloper-Mould, K.E. and Hicke, L. (2000) Monoubiquitin carries a novel internalization signal that is appended to activated receptors. The EMBO Journal, 19, 187-198.
[6] Palma, L., Crinelli, R., Bianchi, M. and Magnani, M. (2009) De-ubiquitylation is the most critical step in the ubiquitin-mediated homeostatic control of the NF-kappaB/IKK basal activity. Molecular and Cellular Biochemistry, 331, 69-80.
[7] Ryu, K.-Y., Baker, R.T. and Kopito, R.R. (2006) Ubiquitin-specific protease 2 as a tool for quantification of total ubiquitin levels in biological specimens. Analytical Biochemistry, 353, 153-155.
[8] Haas, A.L. and Bright, P.M. (1985) The immunochemical detection and quantitation of intracellular ubiquitin-protein conjugates. The Journal of Biological Chemistry, 260, 12464-12473.
[9] Crinelli, R., et al. (2008) Ubiquitin over-expression promotes E6AP autodegradation and reactivation of the p53/MDM2 pathway in HeLa cells. Molecular and Cellular Biochemistry, 318, 129-145.
[10] Kimura, Y. and Tanaka, K. (2010) Regulatory mechanisms involved in the control of ubiquitin homeostasis. The Journal of Biochemistry (Tokyo), 147, 793-798.
[11] Wiborg, O., et al. (1985) The human ubiquitin multigene family: Some genes contain multiple directly repeated ubiquitin coding sequences. The EMBO Journal, 4, 755-759.
[12] Redman, K.L. and Rechsteiner, M. (1989) Identification of the long ubiquitin extension as ribosomal protein S27a. Nature, 338, 438-440.
[13] Webb, G.C., Baker, R.T., Coggan, M. and Board, P.G. (1994) Localization of the human UBA52 ubiquitin fusion gene to chromosome band 19p13.1-p12. Genomics, 19, 567-569. http://dx.doi.org/10.1006/geno.1994.1108
[14] Webb, G.C., Baker, R.T., Fagan, K. and Board, P.G. (1990) Localization of the human UbB polyubiquitin gene to chromosome band 17p11.1-17p12. The American Journal of Human Genetics, 46, 308-315.
[15] Board, P.G., Coggan, M., Baker, R.T., Vuust, J. and Webb, G.C. (1992) Localization of the human UBC polyubiquitin gene to chromosome band 12q24.3. Genomics, 12, 639-642.
[16] Monia, B.P., et al. (1989) Gene synthesis, expression, and processing of human ubiquitin carboxyl extension proteins. The Journal of Biological Chemistry, 264, 4093-4103.
[17] Miller, H.I., et al. (1989) Cloning and expression of a yeast ubiquitin-protein cleaving activity in Escherichia coli. Nature Biotechnology, 7, 698-704.
[18] Tobias, J.W. and Varshavsky, A. (1991) Cloning and functional analysis of the ubiquitin-specific protease gene UBP1 of Saccharomyces cerevisiae. The Journal of Biological Chemistry, 266, 12021-12028.
[19] Wilkinson, K.D., et al. (1989) The neuron-specific protein PGP 9.5 is a ubiquitin carboxyl-terminal hydrolase. Science, 246, 670-673.
[20] Bond, U. and Schlesinger, M.J. (1985) Ubiquitin is a heat shock protein in chicken embryo fibroblasts. Molecular and Cellular Biology, 5, 949-956.
[21] Finley, D., Ozkaynak, E. and Varshavsky, A. (1987) The yeast polyubiquitin gene is essential for resistance to high temperatures, starvation, and other stresses. Cell, 48, 1035-1046.
[22] Fornace Jr., A.J., Alamo Jr., I., Hollander, M.C. and Lamoreaux, E. (1989) Ubiquitin mRNA is a major stress-induced transcript in mammalian cells. Nucleic Acids Research, 17, 1215-1230.
[23] Finch, J.S., et al. (1992) Overexpression of three ubiquitin genes in mouse epidermal tumors is associated with enhanced cellular proliferation and stress. Cell Growth & Differentiation: The Molecular Biology Journal of the American Association for Cancer Research, 3, 269-278.
[24] Nenoi, M. (1992) Induced accumulation of polyubiquitin gene transcripts in HeLa cells after UV-irradiation and TPA-treatment. International Journal of Radiation Biology, 61, 205-211.
[25] Arnason, T. and Ellison, M.J. (1994) Stress resistance in Saccharomyces cerevisiae is strongly correlated with assembly of a novel type of multiubiquitin chain. Molecular and Cellular Biology, 14, 7876-7883.
[26] Fernandes, R., Ramalho, J. and Pereira, P. (2006) Oxidative stress upregulates ubiquitin proteasome pathway in retinal endothelial cells. Molecular Vision, 12, 1526-1535.
[27] Hanna, J., Leggett, D.S. and Finley, D. (2003) Ubiquitin depletion as a key mediator of toxicity by translational inhibitors. Molecular and Cellular Biology, 23, 9251-9261. http://dx.doi.org/10.1128/MCB.23.24.9251-9261.2003
[28] Tsirigotis, M., Zhang, M., Chiu, R.K., Wouters, B.G. and Gray, D.A. (2001) Sensitivity of mammalian cells expressing mutant ubiquitin to protein-damaging agents. The Journal of Biological Chemistry, 276, 46073-46078.
[29] Ryu, K.-Y., et al. (2007) The mouse polyubiquitin gene UbC is essential for fetal liver development, cell-cycle progression and stress tolerance. The EMBO Journal, 26, 2693-2706. http://dx.doi.org/10.1038/sj.emboj.7601722
[30] Nenoi, M., et al. (1996) Heterogeneous structure of the polyubiquitin gene UbC of HeLa S3 cells. Gene, 175, 179-185.
[31] Marinovic, A.C., Zheng, B., Mitch, W.E. and Price, S.R. (2002) Ubiquitin (UbC) expression in muscle cells is increased by glucocorticoids through a mechanism involving Sp1 and MEK1. The Journal of Biological Chemistry, 277, 16673-16681.
[32] Bailey, J.L., et al. (1996) The acidosis of chronic renal failure activates muscle proteolysis in rats by augmenting transcription of genes encoding proteins of the ATP-dependent ubiquitin-proteasome pathway. urnal of Clinical Investigation, 97, 1447-1453.
[33] Mitch, W.E., et al. (1999) Evaluation of signals activating ubiquitin-proteasome proteolysis in a model of muscle wasting. American Journal of Physiology, 276, C1132-C1138.
[34] Marinovic, A.C., Zheng, B., Mitch, W.E. and Price, S.R. (2007) Tissue-specific regulation of ubiquitin (UbC) transcription by glucocorticoids: In vivo and in vitro analyses. American Journal of Physiology—Renal Physiology, 292, F660-F666. http://dx.doi.org/10.1152/ajprenal.00178.2006
[35] Mao, X., et al. (2007) A chemical biology screen identifies glucocorticoids that regulate c-maf expression by increasing its proteasomal degradation through up-regulation of ubiquitin. Blood, 110, 4047-4054.
[36] Kim, D.J., et al. (2004) Peroxisome proliferator-activated receptor beta (delta)-dependent regulation of ubiquitin C expression contributes to attenuation of skin carcinogenesis. The Journal of Biological Chemistry, 279, 23719-23727. http://dx.doi.org/10.1074/jbc.M312063200
[37] Bianchi, M., Crinelli, R., Giacomini, E., Carloni, E. and Magnani, M. (2009) A potent enhancer element in the 5'-UTR intron is crucial for transcriptional regulation of the human ubiquitin C gene. Gene, 448, 88-101.
[38] Sivamani, E. and Qu, R. (2006) Expression enhancement of a rice polyubiquitin gene promoter. Plant Molecular Biology, 60, 225-239.
[39] Bianchi, M., et al. (2013) Yin Yang 1 intronic binding sequences and splicing elicit intron-mediated enhancement of ubiquitin C gene expression. PloS One, 8, e65932.

comments powered by Disqus

Copyright © 2020 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.