First identified in 1975, ubiquitin (Ub) is found as a protein isolated in calf sweetbread, and the assumption was it had something to do with maturing white blood cells. Later found in all tissues of eukaryotic organisms of many species, it was given the name ubiquitin, which derives from the Latin word for “everywhere.” It is a regulatory protein responsible for protein recycling that carries out its responsibilities by binding to proteins and marking them for destruction. This tag directs the tagged proteins to the proteasome complex that degrades and recycles these, or the tag may direct to other proteins for modification, deoxyribonucleic acid (DNA) repair, or gene transcription. It is considered the most conservative of all proteins because its 76 amino acids sequence differs very slightly across all species, whether plant, animal or human.
The process by which this protein marks proteins makes use of three enzymes: E1, which activates Ub and puts it into an reactive state, E2, which then catalyzes the attachment of Ub to proteins, and E3, a ubiquitin-ligase that identifies the protein. In this enzyme cascade, Ub is then capable of dissipating the protein’s protections against proteasomes, so that the proteasome can quickly degrade and destroy it. Accumulations of aberrant proteins within a cell often arise from DNA mutations or mistranslations of genes. As these aberrant proteins can wreak havoc with the functions of a cell, this havoc is believed to be the underlying distress that leads to diseases such as Alzheimer’s, Huntington’s, and Parkinson’s diseases. Making use of proteasome-mediated degradation is one of the ways a cell can achieve repair and expulsion of the aberrant proteins.
When ubiquitin attaches to a protein, it can draw more ubiquitin molecules to the scene to attach as well. These interact with it and sometimes perform modifications such as the destruction of sperm cells after fertilization occurs, regulating the degradation until destruction, or antigen processing and DNA transcriptions and repairs. It has such a large variety of functions within the proteins of a cell that it has led some to believe it has a role in nearly every cellular process. There are also many Ubiquitin-Like proteins (UBLs) that have divergent roles in modifications of cells. One is an interferon-stimulating gene modifier, another is a neuron cell downregulator, and yet another deals with the F antigens in human leukocytes.
Histology departments can use antibodies to this substance to identify cells with abnormal accumulations of aberrant proteins in cells and use these antibodies as disease markers. Research has developed this antigen use to detect neurofibrillary tangles associated with Alzheimer’s, inclusions in motor neuron diseases, and mallory bodies in alcoholic liver disease. There are some genetic disorders associated with ubiquitin. One is a mutation of an E3 ubiquitin-ligase that leads to autosomal-recessive growth retardation called 3M Syndrome. Another is a misregulation and disruption of a gene in Liddle’s Syndrome, which causes hypertension. A gene disruption is also believed to be the cause of Angelman’s Syndrome, once again traced to the E3 ubiquitin-ligase disfunction.
Nearly 50% of all cancerous tumors have been found to be deficient of a particular protein that has been dubbed the “guardian of the genome.” As long as cells can produce this particular gene, cancer is prohibited from developing in a cell. Ubiquitin and its E3 ubiquitin-ligase bonds with this particular protein in a cell and this binding produces a DNA repair of the protein and allows it to recover its viability. The ubiquitin-proteasome system also reduces the size of virus proteins for destruction to aid the body’s immune system. Just in May, 2011, it was announced at the American Association for Cancer Research’s 102nd Convention that the protein's enzyme processes has been linked to assisting the body not to reject chemotherapies in non-small cell lung cancers.