Ubiquitin is a small 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.
Skp, Cullin, F-box containing complex is a multi-protein E3 ubiquitin ligase complex that catalyzes the ubiquitination of proteins destined for 26S proteasomal degradation. Along with the anaphase-promoting complex, SCF has important roles in the ubiquitination of proteins involved in the cell cycle. The SCF complex also marks various other cellular proteins for destruction.
Nuclear factor erythroid 2-related factor 2 (NRF2), also known as nuclear factor erythroid-derived 2-like 2, is a transcription factor that in humans is encoded by the NFE2L2 gene. NRF2 is a basic leucine zipper (bZIP) protein that may regulate the expression of antioxidant proteins that protect against oxidative damage triggered by injury and inflammation, according to preliminary research. In vitro, NRF2 binds to antioxidant response elements (AREs) in the promoter regions of genes encoding cytoprotective proteins. NRF2 induces the expression of heme oxygenase 1 in vitro leading to an increase in phase II enzymes. NRF2 also inhibits the NLRP3 inflammasome.
Cullin 1, also known as CUL1, is a human protein and gene from cullin family. This protein plays an important role in protein degradation and protein ubiquitination.
NEDD8 is a protein that in humans is encoded by the NEDD8 gene. This ubiquitin-like (UBL) protein becomes covalently conjugated to a limited number of cellular proteins, in a process called NEDDylation similar to ubiquitination. Human NEDD8 shares 60% amino acid sequence identity to ubiquitin. The primary known substrates of NEDD8 modification are the cullin subunits of cullin-based E3 ubiquitin ligases, which are active only when NEDDylated. Their NEDDylation is critical for the recruitment of E2 to the ligase complex, thus facilitating ubiquitin conjugation. NEDD8 modification has therefore been implicated in cell cycle progression and cytoskeletal regulation.
RING-box protein 1 is a protein that in humans is encoded by the RBX1 gene.
Cullin-4A is a protein that in humans is encoded by the CUL4A gene. CUL4A belongs to the cullin family of ubiquitin ligase proteins and is highly homologous to the CUL4B protein. CUL4A regulates numerous key processes such as DNA repair, chromatin remodeling, spermatogenesis, haematopoiesis and the mitotic cell cycle. As a result, CUL4A has been implicated in several cancers and the pathogenesis of certain viruses including HIV. A component of a CUL4A complex, Cereblon, was discovered to be a major target of the teratogenic agent thalidomide.
Kelch-like ECH-associated protein 1 is a protein that in humans is encoded by the Keap1 gene.
Cullin-5 is a protein that in humans is encoded by the CUL5 gene.
Cullin-2 is a protein that in humans is encoded by the CUL2 gene.
Ubiquitin D is a protein that in humans is encoded by the UBD gene, also known as FAT10. UBD acts like ubiquitin, by covalently modifying proteins and tagging them for destruction in the proteasome.
Cullin-4B is a protein that in humans is encoded by the CUL4B gene which is located on the X chromosome. CUL4B has high sequence similarity with CUL4A, with which it shares certain E3 ubiquitin ligase functions. CUL4B is largely expressed in the nucleus and regulates several key functions including: cell cycle progression, chromatin remodeling and neurological and placental development in mice. In humans, CUL4B has been implicated in X-linked intellectual disability and is frequently mutated in pancreatic adenocarcinomas and a small percentage of various lung cancers. Viruses such as HIV can also co-opt CUL4B-based complexes to promote viral pathogenesis. CUL4B complexes containing Cereblon are also targeted by the teratogenic drug thalidomide.
RING-box protein 2 is a protein that in humans is encoded by the RNF7 gene.
NEDD8-activating enzyme E1 regulatory subunit is a protein that in humans is encoded by the NAE1 gene.
Cullin-associated NEDD8-dissociated protein 1 is a protein that in humans is encoded by the CAND1 gene.
Cullins are a family of hydrophobic scaffold proteins which provide support for ubiquitin ligases (E3). All eukaryotes appear to have cullins. They combine with RING proteins to form Cullin-RING ubiquitin ligases (CRLs) that are highly diverse and play a role in myriad cellular processes, most notably protein degradation by ubiquitination.
S-phase kinase-associated protein 1 is an enzyme that in humans is encoded by the SKP1 gene.
Kelch-like protein 3 is a protein in humans that is encoded by the KLHL3 gene. Alternative splicing results in multiple transcript variants encoding distinct isoforms.
Raymond Joseph Deshaies is an American biochemist and cell biologist. He is senior vice president of global research at Amgen and a visiting associate at the California Institute of Technology (Caltech). Prior to that, he was a professor of biology at Caltech and an investigator of the Howard Hughes Medical Institute. He is also the co-founder of the biotechnology companies Proteolix and Cleave Biosciences. His research focuses on mechanisms and regulation of protein homeostasis in eukaryotic cells, with a particular focus on how proteins are conjugated with ubiquitin and degraded by the proteasome.
Yi Sun is an American scientist of Chinese origin. He is a molecular biologist and oncologist, and his research is focused on how altered protein Ubiquitylation and Neddylation contribute to cancer development. Sun is a Professor Emeritus of Radiation Oncology at the University of Michigan.
