ArticleThe Journal of biological chemistry2005
Pitx2a binds to human papillomavirus type 18 E6 protein and inhibits E6-mediated P53 degradation in HeLa cells.
Article in The Journal of biological chemistry, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- Molecular Mechanisms of HIV Protease Inhibitors Against HPV-Associated Cervical Cancer: Restoration ofFrontiers in molecular biosciences · 2022Review
- PPI Modulators of E6 as Potential Targeted Therapeutics for Cervical Cancer: Progress and Challenges in Targeting E6.Molecules (Basel, Switzerland) · 2021Review
- Paired-like homeodomain 2B contributes to tumour progression and anti-autophagy in human lung cancer.American journal of cancer research · 2021Article
- Article
- Identification of Deregulated Pathways, Key Regulators, and Novel miRNA-mRNA Interactions in HPV-Mediated Transformation.Cancers · 2020Article
- Identification of the GTPase-activating protein DEP domain containing 1B (DEPDC1B) as a transcriptional target of Pitx2.Experimental cell research · 2015Article
- Identification and characterization of small molecule human papillomavirus E6 inhibitors.ACS chemical biology · 2014Article
- Phosphorylation of myosin II-interacting guanine nucleotide exchange factor (MyoGEF) at threonine 544 by aurora B kinase promotes the binding of polo-like kinase 1 to MyoGEF.The Journal of biological chemistry · 2014Article
- Identification and characterization of small molecule antagonists of pRb inactivation by viral oncoproteins.Chemistry & biology · 2012Article
- Orphan nuclear receptor PNR/NR2E3 stimulates p53 functions by enhancing p53 acetylation.Molecular and cellular biology · 2012Article
- Article
- HPV E6 proteins target Ubc9, the SUMO conjugating enzyme.Virus research · 2011Article
- Role of a novel coiled-coil domain-containing protein CCDC69 in regulating central spindle assembly.Cell cycle (Georgetown, Tex.) · 2010Article
- GIPC1 interacts with MyoGEF and promotes MDA-MB-231 breast cancer cell invasion.The Journal of biological chemistry · 2010Article
- Quantitative model for inferring dynamic regulation of the tumour suppressor gene p53.BMC bioinformatics · 2010Article
- Article
- Molecular Signature of HPV-Induced Carcinogenesis: pRb, p53 and Gene Expression Profiling.Current genomics · 2009Article
- Centrosome/spindle pole-associated protein regulates cytokinesis via promoting the recruitment of MyoGEF to the central spindle.Molecular biology of the cell · 2009Article
- Phosphorylation of MyoGEF on Thr-574 by Plk1 promotes MyoGEF localization to the central spindle.The Journal of biological chemistry · 2008Article
- Testing gene set enrichment for subset of genes: Sub-GSE.BMC bioinformatics · 2008Article
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
Binding of high risk human papillomavirus (HPV) E6 protein to E6-associated protein (E6AP), a cellular ubiquitin-protein ligase, enables E6AP to ubiquitinate p53, leading to p53 degradation in cervical cancer cells such as HeLa cells. Here we report that Pitx2a, a bicoid-type homeodomain transcription factor, can bind to HPV E6 protein and inhibit E6/E6AP-mediated p53 degradation. Deletion of the Pitx2a homeodomain abrogates its ability to bind to HPV E6 protein and to induce p53 accumulation in HeLa cells, suggesting that the homeodomain of Pitx2a is essential for inhibition of E6/E6AP-mediated p53 degradation. Recombinant Pitx2a can also block E6/E6AP-mediated p53 degradation in vitro, indicating that this function of Pitx2a is independent of its transcription activity. Pitx2a does not regulate Hdm2-mediated p53 degradation, because Pitx2a does not affect p53 protein levels in HPV-negative cells, such as HCT116, U2OS, and C33A cells. In addition, Pitx2a-induced p53 is transcriptionally active and maintains its specific DNA binding activity in HeLa cells. Taken together, these findings suggest that, by binding to E6, Pitx2a interferes with E6/E6AP-mediated p53 degradation, leading to the accumulation of functional p53 protein in HeLa cells.
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Registered trials
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