ArticleGenes & development2001
Degradation of p53 by adenovirus E4orf6 and E1B55K proteins occurs via a novel mechanism involving a Cullin-containing complex.
Article in Genes & development, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 276 papers.
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Who cites it
276 citing papers in PubMed, 479 citations in OpenAlex.
- The FACT complex associates with the RPA complex at viral replication compartments to promote adenovirus infection.Journal of virology · 2026Article
- Hepatitis B virus X protein induces E6-associated protein-mediated proteasomal degradation of p53 phosphorylated at Ser-15.The Journal of general virology · 2026Article
- Review
- The adenovirus oncoprotein E1B-55K reshapes epigenetic histone modifications in primary human cells.mBio · 2026Article
- CUL5-mediated ubiquitination in cancer cell therapy: context-dependent roles, molecular networks, and emerging therapeutic avenues.Frontiers in medicine · 2026Review
- Opening the black box: insights into ubiquitin-mediated control of innate antiviral immunity and AI-enhanced therapeutics.Frontiers in immunology · 2026Review
- Genome-replicating HC-AdV: A novel high-capacity adenoviral vector class featuring enhancedMolecular therapy. Methods & clinical development · 2025Article
- Orientia tsutsugamushi modulates p53, the cell cycle, and genotoxicity to maintain its intracellular niche.Nature communications · 2025Article
- Cullin 3-mediated ubiquitination restricts enterovirus D68 replication and is counteracted by viral protease 3C.Journal of virology · 2025Article
- Dynamic Modulation of IRE1α-XBP1 Signaling by Adenovirus.Pathogens (Basel, Switzerland) · 2025Article
- E2A, VA RNA I, and L4-22k adenoviral helper genes are sufficient for AAV production in HEK293 cells.Molecular therapy. Methods & clinical development · 2024Article
- Dynamic modulation of IRE1α-XBP1 signaling by adenovirus.bioRxiv : the preprint server for biology · 2024Article
- The human adenovirus PI3K-Akt activator E4orf1 is targeted by the tumor suppressor p53.Journal of virology · 2024Article
- Polyubiquitylated rice stripe virus NS3 translocates to the nucleus to promote cytosolic virus replication via miRNA-induced fibrillin 2 upregulation.PLoS pathogens · 2024Article
- Pathogenicity and virulence of human adenovirus F41: Possible links to severe hepatitis in children.Virulence · 2023Review
- Identification of Adenovirus E1B-55K Interaction Partners through a Common Binding Motif.Viruses · 2023Article
- Adenovirus E1B-55K controls SUMO-dependent degradation of antiviral cellular restriction factors.Journal of virology · 2023Article
- Adenovirus protein VII binds the A-box of HMGB1 to repress interferon responses.PLoS pathogens · 2023Article
- Virus Infection and mRNA Nuclear Export.International journal of molecular sciences · 2023Review
- Article
216 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 7 institutions in 3 countries.
Funding
Abstract
Although MDM2 plays a major role in regulating the stability of the p53 tumor suppressor protein, other poorly understood MDM2-independent pathways also exist. Human adenoviruses have evolved strategies to regulate p53 function and stability to permit efficient viral replication. One mechanism involves adenovirus E1B55K and E4orf6 proteins, which collaborate to target p53 for degradation. To determine the mechanism of this process, a multiprotein E4orf6-associated complex was purified and shown to contain a novel Cullin-containing E3 ubiquitin ligase that is (1) composed of Cullin family member Cul5, Elongins B and C, and the RING-H2 finger protein Rbx1(ROC1); (2) remarkably similar to the von Hippel-Lindau tumor suppressor and SCF (Skp1-Cul1/Cdc53-F-box) E3 ubiquitin ligase complexes; and (3) capable of stimulating ubiquitination of p53 in vitro in the presence of E1/E2 ubiquitin-activating and -conjugating enzymes. Cullins are activated by NEDD8 modification; therefore, to determine whether Cullin complexes are required for adenovirus-induced p53 degradation, studies were conducted in ts41 Chinese hamster ovary cells that are temperature sensitive for the NEDD8 pathway. E4orf6/E1B55K failed to induce the degradation of p53 at the nonpermissive temperature. Thus, our results identify a novel role for the Cullin-based machinery in regulation of p53.
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