Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ubiquitously. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Four genes in the human genome code for ubiquitin: UBB, UBC, UBA52 and RPS27A.
A ubiquitin ligase is a protein that recruits an E2 ubiquitin-conjugating enzyme that has been loaded with ubiquitin, recognizes a protein substrate, and assists or directly catalyzes the transfer of ubiquitin from the E2 to the protein substrate. In simple and more general terms, the ligase enables movement of ubiquitin from a ubiquitin carrier to another protein by some mechanism. The ubiquitin, once it reaches its destination, ends up being attached by an isopeptide bond to a lysine residue, which is part of the target protein. E3 ligases interact with both the target protein and the E2 enzyme, and so impart substrate specificity to the E2. Commonly, E3s polyubiquitinate their substrate with Lys48-linked chains of ubiquitin, targeting the substrate for destruction by the proteasome. However, many other types of linkages are possible and alter a protein's activity, interactions, or localization. Ubiquitination by E3 ligases regulates diverse areas such as cell trafficking, DNA repair, and signaling and is of profound importance in cell biology. E3 ligases are also key players in cell cycle control, mediating the degradation of cyclins, as well as cyclin dependent kinase inhibitor proteins. The human genome encodes over 600 putative E3 ligases, allowing for tremendous diversity in substrates.
Mouse double minute 2 homolog (MDM2) also known as E3 ubiquitin-protein ligase Mdm2 is a protein that in humans is encoded by the MDM2 gene. Mdm2 is an important negative regulator of the p53 tumor suppressor. Mdm2 protein functions both as an E3 ubiquitin ligase that recognizes the N-terminal trans-activation domain (TAD) of the p53 tumor suppressor and as an inhibitor of p53 transcriptional activation.
p14ARF is an alternate reading frame protein product of the CDKN2A locus. p14ARF is induced in response to elevated mitogenic stimulation, such as aberrant growth signaling from MYC and Ras (protein). It accumulates mainly in the nucleolus where it forms stable complexes with NPM or Mdm2. These interactions allow p14ARF to act as a tumor suppressor by inhibiting ribosome biogenesis or initiating p53-dependent cell cycle arrest and apoptosis, respectively. p14ARF is an atypical protein, in terms of its transcription, its amino acid composition, and its degradation: it is transcribed in an alternate reading frame of a different protein, it is highly basic, and it is polyubiquinated at the N-terminus.
S-phase kinase-associated protein 2 is an enzyme that in humans is encoded by the SKP2 gene.
Nucleophosmin (NPM), also known as nucleolar phosphoprotein B23 or numatrin, is a protein that in humans is encoded by the NPM1 gene.
Tumor susceptibility gene 101, also known as TSG101, is a human gene that encodes for a cellular protein of the same name.
F-box/WD repeat-containing protein 1A (FBXW1A) also known as βTrCP1 or Fbxw1 or hsSlimb or pIkappaBalpha-E3 receptor subunit is a protein that in humans is encoded by the BTRC gene.
Protein Mdm4 is a protein that in humans is encoded by the MDM4 gene.
Ubiquitin-specific-processing protease 7 (USP7), also known as ubiquitin carboxyl-terminal hydrolase 7 or herpesvirus-associated ubiquitin-specific protease (HAUSP), is an enzyme that in humans is encoded by the USP7 gene.
60S ribosomal protein L11 is a protein that in humans is encoded by the RPL11 gene.
Ribosome biogenesis protein BOP1 is a protein that in humans is encoded by the BOP1 gene. It is a WD40 repeat-containing nucleolar protein involved in rRNA processing, thereby controlling the cell cycle. It is required for the maturation of the 25S and 5.8S ribosomal RNAs. It may serve as an essential factor in ribosome formation that coordinates processing of the spacer regions in pre-rRNA.
RING finger and CHY zinc finger domain-containing protein 1 is a protein that in humans is encoded by the RCHY1 gene.
SUMO1/sentrin/SMT3 specific peptidase 3, also known as SENP3, is a protein which in humans is encoded by the SENP3 gene.
40S ribosomal protein S25 (eS25) is a protein that in humans is encoded by the RPS25 gene.
Large ribosomal subunit protein uL14 is a protein that in humans is encoded by the RPL23 gene.
Denticleless protein homolog is a protein that in humans is encoded by the DTL gene.
Ribosome biogenesis protein WDR12 is a protein that in humans is encoded by the WDR12 gene on chromosome 2. It is ubiquitously expressed in many tissues and cell types. WDR12 participates in ribosome biogenesis and cell proliferation as a component of the PeBoW complex. This protein is associated with cardiovascular diseases such as coronary artery disease and myocardial infarction. The PCSK9 gene also contains one of 27 loci associated with increased risk of coronary artery disease.
WD repeat-containing protein 26 is a protein that in humans is encoded by the WDR26 gene.
WRAP53 is a gene implicated in cancer development. The name was coined in 2009 to describe the dual role of this gene, encoding both an antisense RNA that regulates the p53 tumor suppressor and a protein involved in DNA repair, telomere elongation and maintenance of nuclear organelles Cajal bodies.
