DISCOVERy OF THE ROLE OF UBIQUITIN IN PROTEIN DEGRADATION HISTORICAL FACTS Courtesy of Sam Griffiths-Jones. Used with permission Source: \Peptide models for protein beta-sheets hD thesis, University of Nottingham, 2001 8(1975)Ubiquitin was first isolated by Gideon Goldstein and colleagues from the thymus(reason why it was originally thought to be a thymic hormone)
Images removed due to copyright considerations See Fig. 2 in David J. Katzmann, Greg Odorizzi Scott D. Emr RECEPTOR DOWNREGULATION AND MULTIVESICULAR-BODY SORTING Nature Reviews Molecular Cell Biology 3, 893-905(2002); doi: 10.1038/nrm973 See Fig. 7 in: Katzmann DJ, Stefan CJ, Babst M, Emr SD
How p53 and Rb pathway function may be disrupted in cancer cells Components of the pathway which are found altered in human cancers are shown in red on the diagram above p53 and Rb themselves may be inactivated by gene mutation (loss of both copies or also as in familial retinoblastoma and Li-Fraumeni syndrome where there are inherited mutations in one copy of Rb or p53 gene respectively. Alternatively
Epstein-Barr virus (EBV), is the herpesvirus that causes infectious mononucleosis and is associated with a number of cancers, particularly lymphomas in immunosuppressed persons including persons with AIDS EBV is a ubiquitous virus, so common that it has been difficult to determine whether it is the cause of certain diseases or whether it is simply there as an artifact
PROTACS: CHIMERIC MOLECULES TO TARGET PROTEINS FOR UBIQUITINATION AND (taken from KM Sakamoto, Mol. Genetics and Metabolism 77(2002)44-56) target targettargettarget target target target target target To circumvent the problem of transducing cells at
insolubility. Administration of cystamine, a transglutaminase inhibitor, reduces the To date, 10 neurological diseases, including aggregate formation, retarding the Huntington's and several ataxias, are caused development of neurological phenotype and by the lengthening of glutamine(@) tracts in prolonging the life span of brain cells in various proteins with no obvious functional or transgenic mouse models
