Advances in Bioscience and Biotechnology, 2013, 4, 1057-1062 ABB http://dx.doi.org/10.4236/abb.2013.412141 Published Online December 2013 (http://www.scirp.org/journal/abb/ ) Ubiquitin C gene: Structure, function, and transcriptional regulation Lucia Radici * , Marzia Bianchi, Rita Crinelli, Mauro Magnani Department of Biomolecular Sciences, Biochemistry and Molecular Biology Section, University of Urbino “Carlo Bo”, Urbino, Italy Email: * radici.lucia@gmail.com , marzia.bianchi@uniurb.it Received 10 October 2013; revised 12 November 2013; accepted 27 November 2013 Copyright © 2013 Lucia Radici et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. ABSTRACT 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 re- ported 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 regula- tion. Starting from the first evidences which circum- scribed the genomic region, pointing out both basic promoter marks (such as transcription start site and TATA-like element), and transcript structure (exon- intron boundaries) we go through more detailed mo- lecular 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. Keywords: Ubiquitin C; Transcriptional Regulation; YY1; Sp1; Ubiquitin Homeostasis 1. INTRODUCTION Ubiquitin (Ub) is a highly conserved 76 amino acid pro- tein which can be conjugated to other proteins via an isopeptide linkage between the carboxy-terminal glycine residue of ubiquitin and the ε-amino group of a lysine within the target protein or it can make an isopeptide bond with a lysine in another moiety of ubiquitin to form Ub chains. This post-translational modification is known to play a central role in the regulation of various cellular processes: the number and placement of Ub molecules added to a protein help to determine its fate. The effects of ubiquitination of a target protein range from the well-known protein degradation through the 26S protea- some, to protein trafficking, cell-cycle regulation, DNA repair, apoptosis and signal transduction [1-6]. Ubiquitin is one of the most abundant protein in eukaryotic cells, constituting 0.1% - 5% of total proteins but, despite its pervasive use and large number of substrates which are ubiquitinated in a cell, Ub does not seem to be pro- duced in excess, rather the free pool of Ub is maintained at an adequate level depending on cell conditions [7-9]. Ubiquitin homeostasis is maintained through different mechanisms: recycling of ubiquitin chains by deubiquit- inating enzymes (DUBs) and de novo synthesis (“Figure 1”) [10]. 2. UBIQUITIN GENES Ubiquitin is encoded in the genome by a family of loci. Two of these genes, UBA52 and RPS27a code for a sin- gle copy of ubiquitin fused to the ribosomal proteins L40 and S27a whereas UbB and UbC are polyubiquitin genes and encode 3 and 9 head-to-tail repeats of ubiquitin, re- spectively These genes were first characterized by Wi- borg et al. in 1985 [11] using Northern blotting analysis of poly(A)-containing RNA from different tissues, but only few years later they were localized in the genome and fully characterized [12-15]. Peculiarity of Ub genes is the process they undergo to obtain free ubiquitin monomers. The first hypothesis was mRNA processing, but it was ruled out since polyubiquitin and ribosomal- fusion transcripts displayed molecular weights on north- ern blot corresponding to the molecular weights pre- dicted from their genes [11]. In 1989, Monia et al. ex- pressed UBA52 and RPS27a in Saccharomyces cere- visiae and demonstrated that the mechanism responsible for generating the free ubiquitin monomer in eukaryotic cells was a proteolytic process involving specific en- zymes [16]. In the same year, the first DUBs were iden- tified, cloned and purified based on the ability to hydrolyze * Corresponding author. OPEN ACCESS