Reconstitution of p53-ubiquitinylation reactions from purified components: the role of human ubiquitin-conjugating enzyme UBC4 and E6-associated...

Abstract

The E6 protein of the high-risk human papillomaviruses inactivates the tumor suppressor protein p53 by stimulating its ubiquitinylation and subsequent degradation. Ubiquitinylation is a multistep process involving a ubiquitin-activating enzyme, one of many distinct ubiquitin-conjugating enzymes, and in certain cases, a ubiquitin ligase. In human papillomavirus-infected cells, E6 and the E6-associated protein are thought to act as a ubiquitin-protein ligase in the ubiquitinylation of p53. Here we describe the cloning of a human ubiquitin-conjugating enzyme that specifically ubiquitinylates E6-associated protein. Furthermore, we define the biochemical pathway of p53 ubiquitinylation and demonstrate that in vivo inhibition of various components in the pathway leads to an inhibition of E6-stimulated p53 degradation.

Keywords

UbiquitinUbiquitin ligaseUbiquitin-conjugating enzymeUbiquitin-Protein LigasesEnzymeDNA ligaseBiologyBiochemistryMolecular biologyCell biologyGene

Affiliated Institutions

Genomic (Brazil) BR

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Publication Info

Year: 1995
Type: article
Volume: 92
Issue: 8
Pages: 3264-3268
Citations: 116
Access: Closed

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APA Style

                            
                                
                                    Mark Rolfe, 
                                
                                    Peggy Beer‐Romero, 
                                
                                    Susan Glass
                                
                                et al.
                            
                            (1995). 
                            Reconstitution of p53-ubiquitinylation reactions from purified components: the role of human ubiquitin-conjugating enzyme UBC4 and E6-associated protein (E6AP).. 
                            Proceedings of the National Academy of Sciences
                            , 92
                            (8)
                            , 3264-3268.
                            https://doi.org/10.1073/pnas.92.8.3264
                        

Identifiers

DOI: 10.1073/pnas.92.8.3264