The DOI matches its Crossref record; 60 of the 61 references it cites were found in a registry or an index, and 1 are not checked yet; none of the 38 sources its claims cite is checked for support yet.
Identification of a novel telomerase repressor that interacts with the human papillomavirus type-16 E6/E6-AP complex
Open accessAbstract
The critical immortalizing activity of the human papillomavirus (HPV) type-16 E6 oncoprotein is to induce expression of hTERT, the catalytic and rate-limiting subunit of telomerase. Additionally, E6 binds to a cellular protein called E6-associated protein (E6-AP) to form an E3 ubiquitin ligase that targets p53 for proteasome-dependent degradation. Although telomerase induction and p53 degradation are separable and distinct functions of E6, binding of E6 to E6-AP strongly correlated with the induction of hTERT. Here, we demonstrate using shRNAs to reduce E6-AP expression that E6-AP is required for E6-mediated telomerase induction. A yeast two-hybrid screen to find new targets of the E6/E6-AP E3 ubiquitin ligase complex identified NFX1. Two isoforms of NFX1 were found: NFX1-123, which coactivated with c-Myc at the hTERT promoter, and NFX1-91, which repressed the hTERT promoter. NFX1-91 was highly ubiquitinated and destabilized in epithelial cells expressing E6. Furthermore, knockdown of NFX1-91 by shRNA resulted in derepression of the endogenous hTERT promoter and elevated levels of telomerase activity. We propose that the induction of telomerase by the HPV-16 E6/E6-AP complex involves targeting of NFX1-91, a newly identified repressor of telomerase, for ubiquitination and degradation.
Checked 2026-11-12 · 1 reference not checked yet
Overview
CoChat Summary
Written by AI from the paper’s full text.
TL;DR
HPV-16 E6 induces hTERT/telomerase, and this paper shows E6-AP is required for that induction. A yeast two-hybrid screen identified NFX1; its NFX1-91 isoform represses the hTERT promoter and is preferentially bound, ubiquitinated, and destabilized by the E6/E6-AP complex.
Key findings
- E6-AP is required for E6-mediated telomerase induction: shRNA against E6-AP reduced E6-AP RNA to ∼29% of vector control, abrogated E6-mediated p53 degradation, and disrupted E6-mediated hTERT induction and TRAP activity in HFKs.
- NFX1 has two splice isoforms with opposing hTERT promoter activities: NFX1-123 coactivated with c-Myc, whereas NFX1-91 repressed the hTERT promoter, reducing activity to ∼60% of background alone and robustly repressing c-Myc induction.
- NFX1-91 is preferentially targeted by E6/E6-AP: E6 expression reduced NFX1-91 half-life ∼46%, from 2.5 h to 1.3 h; MG-132 restored levels; NFX1-91 was highly ubiquitinated, and E6 coimmunoprecipitated preferentially with NFX1-91 rather than NFX1-123.
- NFX1-91 knockdown derepressed endogenous hTERT and increased telomerase activity; E6-expressing cells with reduced NFX1-91 showed greater than twofold increased hTERT by RT-PCR and TRAP, and reduced E6-AP increased NFX1-91 half-life from 1.2 to 1.7 h.
Methods
- Primary human foreskin keratinocytes (HFKs) and 293T, HeLa, C33A, and U2OS cells were used with retroviral shRNA/expression constructs; a yeast two-hybrid screen used catalytically defective E6-AP C833A plus E6 against fetal brain and HeLa cDNA libraries.
- Functional assays included hTERT luciferase reporter assays (710 and 219 constructs), EMSA with recombinant His-tagged NFX1 fragments, RT-PCR, TRAP telomerase assays, Western blotting, cycloheximide and pulse-chase half-life measurements, immunoprecipitation, in vivo ubiquitination assays, and SAβ-galactosidase staining.
- Analyses compared promoter activity, protein stability, ubiquitination, and telomerase activity across vector, E6, E6 mutant, and shRNA conditions; data are presented as representative experiments or averages with error bars where indicated.
Limitations
- The paper states that NFX1-91 did not overexpress well despite repeated attempts, so the authors could not demonstrate hTERT promoter repression by increased NFX1-91 expression.
- The paper states that the reciprocal coimmunoprecipitation to precipitate AU1-16E6 with NFX1 antibody did not work, and that no significant telomere-length differences were observed despite increased telomerase activity.
- The paper states that whether NFX1-123 coactivation is integral to E6-mediated hTERT induction remains to be tested, and future efforts will determine whether either NFX1 isoform is differentially bound in vivo in E6-expressing cells.
- Evident from the text: several key binding and overexpression results are supported by “data not shown,” and the model relies heavily on transient assays, shRNA knockdown, and primary HFK systems rather than in vivo tumor models.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
48 Own result · 17 Own interpretation · 12 Check pending · 7 No full text of the sources · 3 Own method · 2 Sources not found · 1 Not checked yet
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Here, we demonstrate using shRNAs to reduce E6-AP expression that E6-AP is required for E6-mediated telomerase induction.”
- Also stated in: § Results · boosted
“These experiments demonstrated that E6AP expression was required for hTERT induction by HPV-16 E6.”
boostedstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Results · boosted
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Additional in vitro E6/ E6-AP binding studies (data not shown), as well as published data (Table 1), revealed a strong correlation between E6 binding to E6-AP and telomerase activation.”
boostedstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“NFX1-123 strongly coactivated with c-Myc at the hTERT promoter, whereas NFX1-91 repressed the activity of the promoter.”
boostedstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This gene actually encoded two splice variants, NFX1123 and NFX1-91 , with opposing activities in hTERT reporter assays (Fig. 2).”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“NFX1-123 strongly coactivated with c-Myc at the hTERT promoter, whereas NFX1-91 repressed the activity of the promoter.”
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 25
- Probably not a substantial claim. 19
- The quote only partly states this claim. 2
Create a free account to see these claims.
Create a free account to see these assumptions.
49 more claims
Create a free account to see all 90 claims and to verify the 20 references still open.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Plasmids
“Briefly, oligos containing the 26- to 29-nt shRNA sequence were used in PCR reactions”
§ Plasmids
“The n91sh construct was targeted to the 3 ′ UTR region (5 ′ -TGTGGAACCAGCCCAACTGCCCATCAGTCAA3 ′ ).”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ NFX1-91 binds a putative X box in the proximal promoter of hTERT
“HFK/LXSN and HFK/E6 cells were treated with 25 µg/mL cycloheximide for the indicated time points.”
§ Proteasome inhibition and cycloheximide treatment
“For half-life analysis, HFKs were treated with 25 µM cycloheximide (Calbiochem) and harvested in WE16th lysis buffer at the indicated time points.”
Citations
Cites
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477
A DNA damage checkpoint response in telomere-initiated senescence
Fagagna, F. D. D., Reaper, P. M., Clay-Farrace, L., Fiegler, H., Carr, P., von Zglinicki, T., Saretzki, G., Carter, N. P., & Jackson, S. P. (2003) · Nature · doi:10.1038/nature02118 · Cited by 2,917 · cited 1×
“Cells respond to the chromosome ends as though they are a double-stranded DNA break and generally attempt to repair the exposed chromosome ends or initiate a senescent arrest (Espejel and Blasco 2002; d’Adda di Fagagna et al. 2003; Takai et al. 2003).”
BackgroundCreation of human tumour cells with defined genetic elements
Hahn, W. C., Counter, C. M., Lundberg, A. S., Beijersbergen, R. L., Brooks, M. W., & Weinberg, R. A. (1999) · Nature · doi:10.1038/22780 · Cited by 2,345
The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53
Scheffner, M., Huibregtse, J. M., Vierstra, R. D., & Howley, P. M. (1993) · Cell · doi:10.1016/0092-8674(93)90384-3 · Cited by 2,054
Short hairpin RNAs (shRNAs) induce sequence-specific silencing in mammalian cellsPreprint
Paddison, P. J., Caudy, A. A., Bernstein, E., Hannon, G. J., & Conklin, D. S. (2002) · Genes & Development · doi:10.1101/gad.981002 · Cited by 1,571
DNA Damage Foci at Dysfunctional Telomeres
Takai, H., Smogorzewska, A., & de Lange, T. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00542-6 · Cited by 1,409
Hemann, M. T., Strong, M. A., Hao, L.-Y., & Greider, C. W. (2001) · Cell · doi:10.1016/s0092-8674(01)00504-9 · Cited by 1,219
Kiyono, T., Foster, S. A., Koop, J. I., McDougall, J. K., Galloway, D. A., & Klingelhutz, A. J. (1998) · Nature · doi:10.1038/23962 · Cited by 1,206
Self-citationInhibition of telomerase limits the growth of human cancer cells
Hahn, W. C., Stewart, S. A., Brooks, M. W., York, S. G., Eaton, E. N., Kurachi, A. L., Beijersbergen, R. L., Knoll, J. H. M., Meyerson, M. M., & Weinberg, R. A. (1999) · Nature Medicine · doi:10.1038/13495 · Cited by 1,038
RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination
Lorick, K. L., Jensen, J. P., Fang, S., Ong, A. M., Hatakeyama, S., & Weissman, A. M. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.20.11364 · Cited by 981
Research works printed but not linked: 6
- 1996, Cancer Res., 56, 4620
- 2000, Cancer Res., 60, 537
- 1999, Cancer Res., 59, 6087
- 1999, Cancer Res., 59, 826
- 2000, Clin. Cancer Res., 6, 1239
- 1999, Cancer Res., 59, 551
Cited by
Items 101–200 of 277
Exploring the “Other” subfamily of HECT E3-ligases for therapeutic intervention
Singh, S., Ng, J. D., & Sivaraman, J. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107809 · Cited by 37
Ubiquitin ligase E6-AP and its role in human disease
Matentzoglu, K., & Scheffner, M. (2008) · Biochemical Society Transactions · doi:10.1042/bst0360797 · Cited by 37
Proteomic Landscape of Patient-Derived CD4+ T Cells in Recent-Onset Type 1 Diabetes
Lepper, M. F., Ohmayer, U., von Toerne, C., Maison, N., Ziegler, A., & Hauck, S. M. (2017) · Journal of Proteome Research · doi:10.1021/acs.jproteome.7b00712 · Cited by 36
The human papillomavirus E6 protein targets apoptosis-inducing factor (AIF) for degradation
Shimada, M., Yamashita, A., Saito, M., Ichino, M., Kinjo, T., Mizuki, N., Klinman, D. M., & Okuda, K. (2020) · Scientific Reports · doi:10.1038/s41598-020-71134-3 · Cited by 36
Qiu, H., Huang, J., Xiang, C., Li, R., Zuo, E., Zhang, Y., Li, S., & Cheng, X. (2020) · Technology in Cancer Research & Treatment · doi:10.1177/1533033820980112 · Cited by 36
Branca, M., Giorgi, C., Ciotti, M., Santini, D., Bonito, L. D., Costa, S. P. S., Benedetto, A., Bonifacio, D., Bonito, P. D., Paba, P., et al. (2006) · Diagnostic Cytopathology · doi:10.1002/dc.20554 · Cited by 36
Consensus transcriptional regulatory networks of coronavirus-infected human cells
Ochsner, S. A., Pillich, R., & McKenna, N. J. (2020) · Scientific Data · doi:10.1038/s41597-020-00628-6 · Cited by 36
Warts, cancer and ubiquitylation: lessons from the papillomaviruses.
Howley, P. M. (2006) · Europe PMC (PubMed Central) · Cited by 35
Muench, P., Hiller, T., Probst, S., Florea, A., Stubenrauch, F., & Iftner, T. (2009) · Virology · doi:10.1016/j.virol.2009.02.018 · Cited by 34
Togtema, M., Jackson, R., Richard, C., Niccoli, S., & Zehbe, I. (2015) · Virology · doi:10.1016/j.virol.2015.07.025 · Cited by 34
Buchholz, S., Müller‐Schiffmann, A., Matentzoglu, K., Scheffner, M., & Steger, G. (2007) · Journal of General Virology · doi:10.1099/vir.0.83123-0 · Cited by 33
Activation of telomerase by HPVs
Katzenellenbogen, R. A. (2016) · Virus Research · doi:10.1016/j.virusres.2016.11.003 · Cited by 33
TIP60 represses telomerase expression by inhibiting Sp1 binding to the TERT promoter
Rajagopalan, D., Pandey, A. K., Xiuzhen, M. C., Lee, K. K., Hora, S., Zhang, Y., Chua, B. H., Kwok, H. S., Bhatia, S. S., Deng, L., et al. (2017) · PLoS Pathogens · doi:10.1371/journal.ppat.1006681 · Cited by 33
Rataj, O., Haedicke, J., Stubenrauch, F., & Iftner, T. (2018) · International Journal of Cancer · doi:10.1002/ijc.31986 · Cited by 32
Structure and putative function of NFX1‐like proteins in plants
Müssig, C., Schröder, F., Usadel, B., & Lisso, J. (2010) · Plant Biology · doi:10.1111/j.1438-8677.2009.00303.x · Cited by 32
Teissier, S., Khalifa, Y. B., Mori, M., Pautier, P., Desaintes, C., & Thierry, F. (2007) · Journal of Virology · doi:10.1128/jvi.00427-07 · Cited by 32
Regulation of Telomere Homeostasis during Epstein-Barr virus Infection and Immortalization
Kamranvar, S. A., & Masucci, M. G. (2017) · Viruses · doi:10.3390/v9080217 · Cited by 31
Ghanaat, M., Goradel, N. H., Arashkia, A., Ebrahimi, N., Ghorghanlu, S., Malekshahi, Z. V., Fattahi, E., Negahdari, B., & Kaboosi, H. (2021) · Acta Pharmacologica Sinica · doi:10.1038/s41401-021-00616-5 · Cited by 31
de Wilde, J., Wilting, S. M., Meijer, C. J. L. M., van de Wiel, M. A., Ylstra, B., Snijders, P. J. F., & Steenbergen, R. D. M. (2007) · International Journal of Cancer · doi:10.1002/ijc.23210 · Cited by 31
Rangel-Zúñiga, O. A., Camargo, A., Marín, C., Peña‐Orihuela, P. J., Pérez‐Martínez, P., Delgado‐Lista, J., González-Guardia, L., Yubero‐Serrano, E. M., Tinahones, F. J., Malagón, M. M., et al. (2015) · BMC Genomics · doi:10.1186/s12864-015-1725-8 · Cited by 30
Chlon, T. M., Hoskins, E. E., Mayhew, C. N., Wikenheiser‐Brokamp, K. A., Davies, S. M., Mehta, P. A., Myers, K. C., Wells, J. M., & Wells, S. I. (2014) · Journal of Virology · doi:10.1128/jvi.01533-14 · Cited by 30
Redox control of viral carcinogenesis: The human papillomavirus paradigm
Foppoli, C., Marco, F. D., Cini, C., & Marzia Perluigi, A. (2014) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2014.12.016 · Cited by 30
Regulation of Telomerase by Human PapillomavirusesPreprint
Galloway, D. A., Gewin, L. C., Myers, H. E., LUO, W., Grandori, C., Katzenellenbogen, R. A., & McDougall, J. K. (2005) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2005.70.041 · Cited by 30
Self-citationHuman papillomavirus vaccine: Widening the scope for cancer prevention
No, J. H., Kim, M., Jeon, Y. T., Kim, Y., & Song, Y. S. (2011) · Molecular Carcinogenesis · doi:10.1002/mc.20657 · Cited by 29
Wasserman, P., Rubin, D. S., & Turett, G. S. (2017) · AIDS Patient Care and STDs · doi:10.1089/apc.2017.0063 · Cited by 29
The Molecular Interplay between Human Oncoviruses and Telomerase in Cancer Development
Tornesello, M. L., Cerasuolo, A., Starita, N., Tornesello, A. L., Bonelli, P., Tuccillo, F. M., Buonaguro, L., Isaguliants, M. G., & Buonaguro, F. M. (2022) · Cancers · doi:10.3390/cancers14215257 · Cited by 29
Tanaka (1998) · International Journal of Molecular Medicine · doi:10.3892/ijmm_00000121 · Cited by 29
Requirement of E7 oncoprotein for viability of HeLa cells
Nishimura, A., Nakahara, T., Ueno, T., Sasaki, K., Yoshida, S., Kyo, S., Howley, P. M., & Sakai, H. (2006) · Microbes and Infection · doi:10.1016/j.micinf.2005.10.015 · Cited by 28
Kajitani, N., & Schwartz, S. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2022.02.014 · Cited by 27
Xu, M., Katzenellenbogen, R. A., Grandori, C., & Galloway, D. A. (2013) · Virology · doi:10.1016/j.virol.2013.07.014 · Cited by 27
Self-citationJeda, A. S., Badrzadeh, F., Esghaei, M., & Abdoli, A. (2021) · Cancer Treatment and Research Communications · doi:10.1016/j.ctarc.2021.100323 · Cited by 26
Molecular Mechanisms of MmuPV1 E6 and E7 and Implications for Human Disease
Romero-Masters, J. C., Lambert, P. F., & Münger, K. (2022) · Viruses · doi:10.3390/v14102138 · Cited by 26
Human papillomavirus proteins as prospective therapeutic targets
Pang, C. L., & Thierry, F. (2012) · Microbial Pathogenesis · doi:10.1016/j.micpath.2012.11.002 · Cited by 26
Scarth, J. A., Wasson, C. W., Patterson, M. R., Evans, D., Barba‐Moreno, D., Carden, H., Cassidy, R., Whitehouse, A., Mankouri, J., Samson, A., et al. (2023) · Oncogene · doi:10.1038/s41388-023-02772-w · Cited by 25
Skelin, J., & Tomaić, V. (2023) · Viruses · doi:10.3390/v15112253 · Cited by 25
E6AP ubiquitin ligase mediates ubiquitin‐dependent degradation of peroxiredoxin 1
Nasu, J., Murakami, K., Miyagawa, S., Yamashita, R., Ichimura, T., Wakita, T., Hotta, H., Miyamura, T., Suzuki, T., Satoh, T., et al. (2010) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22752 · Cited by 25
GRIM-19 Disrupts E6/E6AP Complex to Rescue p53 and Induce Apoptosis in Cervical Cancers
Zhou, Y. Y., Wei, Y., Zhu, J., Wang, Q., Bao, L., Ma, Y., Chen, Y., Feng, D., Zhang, A., Sun, J., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0022065 · Cited by 25
Vliet-Gregg, P. A., Hamilton, J. R., & Katzenellenbogen, R. A. (2015) · Virology · doi:10.1016/j.virol.2015.02.002 · Cited by 24
Stefan, M., Portis, T., Longnecker, R., & Nicholls, R. D. (2005) · Genomics · doi:10.1016/j.ygeno.2005.02.004 · Cited by 24
Senescence as a modulator of oral squamous cell carcinoma development
Parkinson, E. K. (2010) · Oral Oncology · doi:10.1016/j.oraloncology.2009.09.009 · Cited by 23
Arizmendi-Izazaga, A., Navarro‐Tito, N., Jiménez‐Wences, H., Evaristo-Priego, A., Priego-Hernández, V. D., Dircio-Maldonado, R., Zacapala-Gómez, A. E., Catalán, M. A. M., Illades‐Aguiar, B., Nova-Ocampo, M. D., et al. (2024) · Current Issues in Molecular Biology · doi:10.3390/cimb46060370 · Cited by 22
NFXL2 modifies cuticle properties in Arabidopsis
Lisso, J., Schröder, F., Schippers, J. H. M., & Müssig, C. (2012) · Plant Signaling & Behavior · doi:10.4161/psb.19838 · Cited by 22
Ganzenmueller, T., Matthaei, M., Muench, P., Scheible, M. H., Iftner, A., Hiller, T., Leiprecht, N., Probst, S., Stubenrauch, F., & Iftner, T. (2007) · Virology · doi:10.1016/j.virol.2007.11.006 · Cited by 22
The Involvement of Human Papilloma Virus in Gastrointestinal Cancers
Baj, J., Forma, A., Dudek, I., Chilimoniuk, Z., Dobosz, M., Dobrzyński, M., Teresiński, G., Buszewicz, G., Flieger, J., & Portincasa, P. (2022) · Cancers · doi:10.3390/cancers14112607 · Cited by 21
Regulation of snoRNAs in Cancer: Close Encounters with Interferon
Nallar, S. C., & Kalvakolanu, D. V. (2013) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2012.0106 · Cited by 21
Vliet-Gregg, P. A., Robinson, K. L., Levan, J., Matsumoto, L. R., & Katzenellenbogen, R. A. (2019) · Cancer Letters · doi:10.1016/j.canlet.2019.02.024 · Cited by 21
Human Papillomavirus E6 and E7 Oncogenes
Münger, K., Howley, P. M., & DiMaio, D. (2007) · Springer eBooks · doi:10.1007/978-0-387-36523-7_10 · Cited by 21
Ma, Y., Hao, S., Wang, S., Zhao, Y., Lim, B., Lei, M., Spector, D. J., El‐Deiry, W. S., Zheng, S.-Y., & Zhu, J. (2015) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-14-0693 · Cited by 20
Anticancer Therapy Targeting Telomeres and Telomerase: Current Status
Parkinson, E. K., & Minty, F. (2007) · BioDrugs · doi:10.2165/00063030-200721060-00005 · Cited by 19
Yamashita, Y., Tsurumi, T., Mori, N., & Kiyono, T. (2006) · Pathology International · doi:10.1111/j.1440-1827.2006.02026.x · Cited by 18
Self-citationThe Human Papillomavirus E7 Proteins Associate with p190RhoGAP and Alter Its Function
Todorovic, B., Nichols, A. C., Chitilian, J. M., Myers, M. P., Shepherd, T. G., Parsons, S. J., Barrett, J. W., Banks, L., & Mymryk, J. S. (2014) · Journal of Virology · doi:10.1128/jvi.03263-13 · Cited by 18
Lisso, J., Schröder, F., Fisahn, J., & Müssig, C. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026982 · Cited by 18
The Relevance of Telomerase and Telomere-Associated Proteins in B-Acute Lymphoblastic Leukemia
da Mota, T. H. A., Camargo, R., Biojone, E. R., Guimarães, A. F. R., Pittella-Silva, F., & de Oliveira, D. M. (2023) · Genes · doi:10.3390/genes14030691 · Cited by 16
Martinelli, C. V., Ercoli, A., Parisi, S., Iatì, G., Pergolizzi, S., Alfano, L., Pentimalli, F., Laurentiis, M. D., Giordano, A., & Cortellino, S. (2025) · BMC Medicine · doi:10.1186/s12916-025-04247-z · Cited by 16
Aco-Tlachi, M., Carreño-López, R., Martínez‐Morales, P., Maycotte, P., Aguilar‐Lemarroy, A., Jave‐Suárez, L. F., Santos‐López, G., Reyes‐Leyva, J., & Vallejo‐Ruiz, V. (2018) · Infectious Agents and Cancer · doi:10.1186/s13027-018-0197-2 · Cited by 16
Tumor viruses and replicative immortality – Avoiding the telomere hurdle
Chen, X., Kamranvar, S. A., & Masucci, M. G. (2014) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2014.01.006 · Cited by 16
Identification of a USP9X Substrate NFX1-123 by SILAC-Based Quantitative Proteomics
Chen, X., Lu, D., Gao, J., Zhu, H., Zhou, Y., Gao, D., & Zhou, H. (2019) · Journal of Proteome Research · doi:10.1021/acs.jproteome.9b00139 · Cited by 16
Tumour virology – history, status and future challenges
Kalland, K.-H., Ke, X., & Oyan, A. M. (2009) · Apmis · doi:10.1111/j.1600-0463.2009.02452.x · Cited by 15
Mutagenic Potential ofBos taurusPapillomavirus Type 1 E6 Recombinant Protein: First Description
Araldi, R. P., Mazzuchelli-de-Souza, J., Módolo, D. G., de Souza, E. B., de Melo, T. C., Spadacci-Morena, D. D., Magnelli, R. F., de Carvalho, M. A. C. R., Júnior, P. L. D. S., de Carvalho, R. F., et al. (2015) · BioMed Research International · doi:10.1155/2015/806361 · Cited by 15
Levan, J., Vliet-Gregg, P. A., Robinson, K. L., & Katzenellenbogen, R. A. (2017) · PLoS ONE · doi:10.1371/journal.pone.0187514 · Cited by 15
Is viral E6 oncoprotein a viable target? A critical analysis in the context of cervical cancer
Kumar, A., Rathi, E., Hariharapura, R. C., & Kini, S. G. (2020) · Medicinal Research Reviews · doi:10.1002/med.21697 · Cited by 14
Update: Immunotherapeutic Strategies in HPV-Associated Head and Neck Squamous Cell Carcinoma
Sun, F., & Colevas, A. D. (2025) · Viruses · doi:10.3390/v17050712 · Cited by 14
Long Noncoding RNAs in HPV-Induced Oncogenesis
Goedert, L. (2016) · Advances in Tumor Virology · doi:10.4137/atv.s29816 · Cited by 13
Genes Regulated by HPV 16 E6 and High Expression of NFX1-123 in Cervical Cancers
Chintala, S., Levan, J., Robinson, K. L., Quist, K. M., & Katzenellenbogen, R. A. (2020) · OncoTargets and Therapy · doi:10.2147/ott.s251926 · Cited by 13
Telomerase: a crucial player in HTLV-I-induced human T-cell leukemia.
Bellon, M., & Nicot, C. (2007) · PubMed · Cited by 13
Noncanonical functions of telomerase and telomeres in viruses‐associated cancer
Rasouli, S., Dakic, A., Wang, Q., Mitchell, D., Blakaj, D. M., Putluri, N., Li, J., & Liu, X. (2024) · Journal of Medical Virology · doi:10.1002/jmv.29665 · Cited by 12
NFX1, Its Isoforms and Roles in Biology, Disease and Cancer
Chintala, S., & Katzenellenbogen, R. A. (2021) · Biology · doi:10.3390/biology10040279 · Cited by 12
Post-Transcriptional Gene Regulation by HPV 16E6 and Its Host Protein Partners
Billingsley, C., Chintala, S., & Katzenellenbogen, R. A. (2022) · Viruses · doi:10.3390/v14071483 · Cited by 12
Ciesielska, U., Nowińska, K., Podhorska‐Okołów, M., & Dzięgiel, P. (2012) · PubMed · Cited by 12
Cervical Cancer Development: Implications of HPV16 E6E7-NFX1-123 Regulated Genes
Quist, K. M., Solorzano, I., Wendel, S. O., Chintala, S., Wu, C., Wallace, N. A., & Katzenellenbogen, R. A. (2021) · Cancers · doi:10.3390/cancers13246182 · Cited by 12
Bovine papillomavirus productive infection in cell cultures: First evidences
Araldi, R. P., de Melo, T. C., Consonni, S. R., de Souza, J. M., Módolo, D. G., Assaf, S. M. R., de Lima, T. A. N., Magnelli, R. F., Spadacci-Morena, D. D., de Carvalho, R. F., et al. (2017) · Virology Research and Reviews · doi:10.15761/vrr.1000110 · Cited by 12
Yang, Y., Liu, W., Zou, W., Wang, H., Zong, H., Jiang, J., Wang, Y., & Gu, J. (2006) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21164 · Cited by 12
Kanda, T., & Kukimoto, I. (2006) · Uirusu · doi:10.2222/jsv.56.219 · Cited by 12
Ghani, F. I., Dendo, K., Watanabe, R., Yamada, K., Yoshimatsu, Y., Yugawa, T., Nakahara, T., Tanaka, K., Yoshida, H., Yoshida, M., et al. (2019) · Cells · doi:10.3390/cells8070644 · Cited by 11
Self-citationMartin, C. A., Sheppard, E. C., Ali, H. A. A., Illera, J. C., Suh, A., Spurgin, L. G., & Richardson, D. S. (2024) · Molecular Ecology · doi:10.1111/mec.17365 · Cited by 11
Levan, J., Vliet-Gregg, P. A., Robinson, K. L., Matsumoto, L. R., & Katzenellenbogen, R. A. (2019) · Virology · doi:10.1016/j.virol.2019.03.008 · Cited by 11
Origin and immunoescape of uterine cervical cancer
Hede, D. V., Langers, I., Delvenne, P., & Jacobs, N. (2014) · La Presse Médicale · doi:10.1016/j.lpm.2014.09.005 · Cited by 11
Xu, J., Fang, Y., Qin, J., Chen, X., Liang, X., Xie, X., & Lü, W. (2016) · FEBS Letters · doi:10.1002/1873-3468.12486 · Cited by 11
Korzeniewski, N., & Duensing, S. M. (2012) · Humana Press eBooks · doi:10.1007/978-1-62703-035-9_12 · Cited by 10
Ewald, P. W., & Ewald, H. A. S. (2019) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2018.0304 · Cited by 10
De-regulation of aurora kinases by oncogenic HPV; implications in cancer development and treatment
Oladipo, K. H., & Parish, J. L. (2025) · Tumour Virus Research · doi:10.1016/j.tvr.2025.200314 · Cited by 9
Bakri, R., Parikesit, A. A., Satriyanto, C. P., Kerami, D., & Tambunan, U. S. F. (2014) · Advances in Bioinformatics · doi:10.1155/2014/104823 · Cited by 9
Telomerase: a good target in hepatocellular carcinoma? An overview of relevant preclinical data
Tornesello, M. L., Tornesello, A. L., Starita, N., Cerasuolo, A., Izzo, F., Buonaguro, L., & Buonaguro, F. M. (2022) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2022.2147062 · Cited by 9
HPV E6, E6AP and Cervical Cancer
Beaudenon, S. L. (2007) · Targeted Protein Database · doi:10.2970/tpdb.2007.67 · Cited by 9
Molecular basis of cervical carcinogenesis by high-risk human papillomaviruses
Yugawa, T., & Kiyono, T. (2008) · Uirusu · doi:10.2222/jsv.58.141 · Cited by 9
Self-citationRetraction Note: Molecular mechanisms in progression of HPV-associated cervical carcinogenesis
Gupta, S. M., & Mania‐Pramanik, J. (2019) · Journal of Biomedical Science · doi:10.1186/s12929-019-0545-6 · Cited by 9
RetractedFrom infection to immortality: The role of HPV and telomerase in head and neck cancer
Giunco, S., Mistro, A. D., Morello, M., Lidonnici, J., Frayle, H., Gori, S., Rossi, A. D., & Boscolo‐Rizzo, P. (2025) · Oral Oncology · doi:10.1016/j.oraloncology.2024.107169 · Cited by 8
Nagy, N., Matskova, L. V., Hellman, U., Klein, G., & Klein, E. (2009) · Cell Cycle · doi:10.4161/cc.8.19.9636 · Cited by 8
Targeting Human Papillomavirus-Associated Cancer by Oncoprotein-Specific Recombinant Antibodies
Donà, M. G., Bonito, P. D., Chiantore, M. V., Amici, C., & Accardi, L. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179143 · Cited by 8
Zhao, Q., Yang, S., Hao, S., Chen, Z., Tang, L., Wu, Z., Wu, J., Xu, M., Ma, Z., Li, Z., et al. (2024) · Journal of Medical Virology · doi:10.1002/jmv.29769 · Cited by 8
Involvement of the NFX1-repressor complex in PKC-δ-induced repression of hTERT transcription
Yamashita, S., Fujii, K., Zhao, C., Takagi, H., & Katakura, Y. (2016) · The Journal of Biochemistry · doi:10.1093/jb/mvw038 · Cited by 8
Oncogenic Viruses, Cellular Transformation and Human Cancers
Zheng, Y., & Ou, J. J. (2009) · WORLD SCIENTIFIC eBooks · doi:10.1142/9789812833471_0001 · Cited by 8
Dayer, G., Masoom, M. L., Togtema, M., & Zehbe, I. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21217980 · Cited by 8
High expression of NFX1 ‐123 in HPV positive head and neck squamous cell carcinomas
Chintala, S., Quist, K. M., Gonzalez‐DeWhitt, P. A., & Katzenellenbogen, R. A. (2021) · Head & Neck · doi:10.1002/hed.26906 · Cited by 8
Palomino-Vizcaíno, G., Bañuelos-Villegas, E. G., & Álvarez-Salas, L. M. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252312991 · Cited by 7
Resolution of oncogene-induced senescence markers in HPV-infected cervical cancer tissue
Khasawneh, A. I., Shboul, S. A., Himsawi, N. M., Rousan, A. A., Shahin, N. A., El‐Sadoni, M., Alhesa, A., Ghalioun, A. A., Khawaldeh, S., Shawish, B., et al. (2025) · BMC Cancer · doi:10.1186/s12885-025-13499-0 · Cited by 7
ZNFX1: a multifunctional modulator of the innate immune response
Cheng, L. Y., & Parker, R. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1564628 · Cited by 7
Assessing the Burden of HPV-Associated Cancers in the United States
Saraiya, M., Benard, V. B., Coughlin, S. S., Flowers, L., Cokkinides, V. E., Schwenn, M. R., Huang, Y., Giuliano, A. R., & Lee, H. (2008) · Cited by 7
Burassakarn, A., Phusingha, P., Yugawa, T., Noguchi, K., Ekalaksananan, T., Vatanasapt, P., Kiyono, T., & Pientong, C. (2022) · Cancers · doi:10.3390/cancers14081944 · Cited by 7
Self-citationThe Effect of Proteasome Inhibition on p53 Degradation and Proliferation in Tonsil Epithelial Cells
Harris, G. F., Anderson, M. E., & Lee, J. H. (2008) · Archives of Otolaryngology - Head and Neck Surgery · doi:10.1001/archoto.2007.37 · Cited by 7
Metadata
- Authors
- Gewin, L., Myers, H., Kiyono, T., & Galloway, D. A.
- Affiliations
- University of Washington (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2004-09-15
- Volume
- 18
- Issue
- 18
- Pages
- 2269-2282
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC517520
- OpenAlex
- W2127352755
- Cited by
- 277
- References
- 60
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 8 · 2023: 8 · 2022: 10 · 2021: 10 · 2020: 14 · 2019: 12 · 2018: 14 · 2017: 11 · 2016: 13 · 2015: 13 · 2014: 13 · 2013: 11 · 2012: 17
- Type
- posted content
- Language
- en
- Open access
- green
- pmc.ncbi.nlm.nih.gov
- Locations
- Genes & Development (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion)
- Funders
- National Cancer Institute (T32CA009229, 5 T32 CA 09229-23, R01CA064795)
- National Institute of Allergy and Infectious Diseases (T32AI007140)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- HPV16, E6 oncoprotein, UBE3A, E3 ubiquitin ligase, hTERT promoter, ubiquitination, p53 degradation, epithelial cells
- MeSH terms
- Amino Acid Sequence, Binding Sites, Cells, Cultured, DNA-Binding Proteins, Enzyme Activation, Humans, Molecular Sequence Data, Mutation, Oncogene Proteins, Viral, Promoter Regions, Genetic, Repressor Proteins, Tumor Suppressor Protein p53, Genes, myc, Telomerase, Protein Isoforms, Ubiquitin-Protein Ligases, Macromolecular Substances
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-11-12, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-12 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
