The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
Inhibition of cyclin D-CDK4/CDK6 activity is associated with an E2F-mediated induction of cyclin kinase inhibitor activity.
Open accessAbstract
Alterations of various components of the cell cycle regulatory machinery that controls the progression of cells from a quiescent to a growing state contribute to the development of many human cancers. Such alterations include the deregulated expression of G1 cyclins, the loss of function of activities such as those of protein p16INK4a that control G1 cyclin-dependent kinase activity, and the loss of function of the retinoblastoma protein (RB), which is normally regulated by the G1 cyclin-dependent kinases. Various studies have revealed an inverse relationship in the expression of p16INK4a protein and the presence of functional RB in many cell lines. In this study we show that p16INK4a is expressed in cervical cancer cell lines in which the RB gene, Rb, is not functional, either as a consequence of Rb mutation or expression of the human papillomavirus E7 protein. We also demonstrate that p16INK4a levels are increased in primary cells in which RB has been inactivated by DNA tumor virus proteins. Given the role of RB in controlling E2F transcription factor activity, we investigated the role of E2F in controlling p16INK4a expression. We found that E2F1 overexpression leads to an inhibition of cyclin D1-dependent kinase activity and induces the expression of a p16-related transcript. We conclude that the accumulation of G1 cyclin-dependent kinase activity during normal G1 progression leads to E2F accumulation through the inactivation of RB, and that this then leads to the induction of cyclin kinase inhibitor activity and a shutdown of G1 kinase activity.
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Cites
The retinoblastoma protein and cell cycle control
Weinberg, R. A. (1995) · Cell · doi:10.1016/0092-8674(95)90385-2 · Cited by 4,862
The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53
Scheffner, M., Werness, B. A., Huibregtse, J. M., Levine, A. J., & Howley, P. M. (1990) · Cell · doi:10.1016/0092-8674(90)90409-8 · Cited by 3,995
Self-citationA new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4.
Serrano, M., Hannon, G. J., & Beach, D. (1993) · Nature · doi:10.1038/366704a0 · Cited by 3,650
The human papilloma virus-16 E7-oncoprotein is able to bind to the retinoblastoma gene product
Dyson, N., Howley, P. M., Münger, K., & Harlow, E. (1989) · Science · doi:10.1126/science.2537532 · Cited by 3,017
A cell cycle regulator potentially involved in genesis of many tumor types
Kamb, A., Gruis, N. A., Weaver-Feldhaus, J., Liu, Q., Harshman, K., Tavtigian, S. V., Stockert, E., Day, R. S., Johnson, B. E., & Skolnick, M. H. (1994) · Science · doi:10.1126/science.8153634 · Cited by 2,751
Association of Human Papillomavirus Types 16 and 18 E6 Proteins with p53
Werness, B. A., Levine, A. J., & Howley, P. M. (1990) · Science · doi:10.1126/science.2157286 · Cited by 2,562
Self-citationpl5INK4B is a potentia| effector of TGF-β-induced cell cycle arrest
Hannon, G. J., & Beach, D. (1994) · Nature · doi:10.1038/371257a0 · Cited by 1,950
Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers
Nobori, T., Miura, K., Wu, D. J., Lois, A., Takabayashi, K., & Carson, D. A. (1994) · Nature · doi:10.1038/368753a0 · Cited by 1,742
Cyclin D1 is a nuclear protein required for cell cycle progression in G1
Baldin, V, Lukas, J., Marcote, M. J., Pagano, M., & Draetta, G. (1993) · Genes & Development · doi:10.1101/gad.7.5.812 · Cited by 1,614
E2F: a Link Between the Rb Tumor Suppressor Protein and Viral Oncoproteins
Nevins, J. R. (1992) · Science · doi:10.1126/science.1411535 · Cited by 1,506
Self-citation
Cited by
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
Forging a signature of in vivo senescence
Sharpless, N. E., & Sherr, C. J. (2015) · Nature Reviews Cancer · doi:10.1038/nrc3960 · Cited by 1,104
The p16INK4a/CDKN2A tumor suppressor and its relatives
Ruas, M., & Peters, G. (1998) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/s0304-419x(98)00017-1 · Cited by 911
Sano, T., Oyama, T., Kashiwabara, K., Fukuda, T., & Nakajima, T. (1998) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)65689-1 · Cited by 579
Klaes, R., Benner, A., Friedrich, T., Ridder, R., Herrington, S., Jenkins, D., Kurman, R. J., Schmidt, D., Stoler, M., & von Knebel Doeberitz, M. (2002) · The American Journal of Surgical Pathology · doi:10.1097/00000478-200211000-00001 · Cited by 461
Metadata
- Authors
- Khleif, S. N., DeGregori, J., Yee, C. L., Otterson, G. A., Kaye, F. J., Nevins, J. R., & Howley, P. M.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1996-04-30
- Volume
- 93
- Issue
- 9
- Pages
- 4350-4354
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1977636641
- Cited by
- 358
- References
- 58
- FWCI
- 3.95
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Inhibition of cyclin D-CDK4/CDK6 activity is associated with an E2F-mediated induction of cyclin kinase inhibitor activity. https://app.cochat.ai/papers/10.1073/pnas.93.9.4350
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- Khleif, S. N., DeGregori, J., Yee, C. L., Otterson, G. A., Kaye, F. J., Nevins, J. R., & Howley, P. M. (1996). Inhibition of cyclin D-CDK4/CDK6 activity is associated with an E2F-mediated induction of cyclin kinase inhibitor activity. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.93.9.4350
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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