Biomaterial Database

Targeting and degradation of p53 by E6 of human papillomavirus type 16 is preferential for the 1620+ p53 conformation. 1993

E A Medcalf, and J Milner

Department of Pathology, University of Cambridge, UK.

E6-mediated degradation of p53 is believed to play a role in the transformation of cells by high-risk types of human papillomavirus. In order to explore the structural requirements for targeting of p53 we have compared E6-mediated degradation of variant p53 forms expressed in vitro. Complete degradation was observed in samples containing monomers, dimers and higher molecular weight structures of wild-type p53, indicating that E6 targets all quaternary forms of wild-type p53. Wild-type human and murine p53s reactive with PAb 1620 (which recognizes a conformation-dependent epitope) were degraded when incubated with E6. Mutant p53 proteins were variably resistant to E6-mediated degradation, and this correlated with PAb 1620 reactivity. Thus, mutants hp53Val-154, hp53Val-266 and hp53Pro-273 (1620 degrees) were completely resistant to degradation, whereas hp53Ile-247 and hp53Trp-248 (1620+) were degraded. Mutants hp53Leu-273 and mp53Val-135, which are temperature sensitive for conformation, were completely degraded in the 1620+ form but degradation resistant in the 1620 degrees form. Although the PAb 1620+ conformation appeared important for recognition of p53 by E6, the epitope itself is unlikely to be the actual recognition target since the PAb 1620 monoclonal antibody failed to protect against E6-mediated degradation.

UI	MeSH Term	Description	Entries
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D009856	Oncogene Proteins, Viral	Products of viral oncogenes, most commonly retroviral oncogenes. They usually have transforming and often protein kinase activities.	Viral Oncogene Proteins,Viral Transforming Proteins,v-onc Proteins,Transforming Proteins, Viral,v onc Proteins
D011487	Protein Conformation	The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).	Conformation, Protein,Conformations, Protein,Protein Conformations
D012097	Repressor Proteins	Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.	Repressor Molecules,Transcriptional Silencing Factors,Proteins, Repressor,Silencing Factors, Transcriptional
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000939	Epitopes	Sites on an antigen that interact with specific antibodies.	Antigenic Determinant,Antigenic Determinants,Antigenic Specificity,Epitope,Determinant, Antigenic,Determinants, Antigenic,Specificity, Antigenic
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D013696	Temperature	The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.	Temperatures
D016159	Tumor Suppressor Protein p53	Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.	p53 Tumor Suppressor Protein,Cellular Tumor Antigen p53,Oncoprotein p53,TP53 Protein,TRP53 Protein,p53 Antigen,pp53 Phosphoprotein,Phosphoprotein, pp53
D017434	Protein Structure, Tertiary	The level of protein structure in which combinations of secondary protein structures (ALPHA HELICES; BETA SHEETS; loop regions, and AMINO ACID MOTIFS) pack together to form folded shapes. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure.	Tertiary Protein Structure,Protein Structures, Tertiary,Tertiary Protein Structures