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Inhibition of CDK activity and PCNA-dependent DNA replication by p21 is blocked by interaction with the HPV-16 E7 oncoprotein
Abstract
p21 inhibits cyclin-dependent kinase (CDK) activity and proliferating cell nuclear antigen (PCNA)-dependent DNA replication by binding to CDK/cyclin complexes and to PCNA through distinct domains. The human papillomavirus (HPV)-16 E7 oncoprotein (16E7) abrogated a DNA damage-induced cell cycle arrest in vivo, despite high levels of p21. Using cell lysates and purified proteins we show that 16E7 prevented p21 both from inhibiting CDK2/cyclin E activity and PCNA-dependent DNA replication, whereas the nononcogenic HPV-6 E7 had reduced effects. Inactivation of both inhibitory functions of p21 was attained through binding between 16E7 and sequences in the carboxy-terminal end of p21 that overlap with the PCNA-binding site and the second p21 cyclin-binding motif. These data imply that the carboxyl terminus of p21 simultaneously modulates both CDK activity and PCNA-dependent DNA replication and that a single protein, 16E7, can override this modulation to disrupt normal cell cycle control.
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“Although E7 expression increases p21Cip1 through protein stabilization [154,155,156], cdk2 remains active in HPV-E7-expressing cells [147,148,157]”
From The Not-So-Good, the Bad and the Ugly: HPV E5, E6 and E7 Oncoproteins in the Orchestration of Carcinogenesis (2021) · cites this paper as [147]
In the citing paper
“HPV-16 E7 abrogates the inhibition of cdk2 activity by interacting with CKIs, p21Cip1 [147,148] and p27Kip1 [149]”
From The Not-So-Good, the Bad and the Ugly: HPV E5, E6 and E7 Oncoproteins in the Orchestration of Carcinogenesis (2021) · cites this paper as [147]
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Cites
Mice Lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control
Deng, C., Zhang, P., Wade Harper, J., Elledge, S. J., & Leder, P. (1995) · Cell · doi:10.1016/0092-8674(95)90039-x · Cited by 2,113
The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA
Waga, S., Hannon, G. J., Beach, D., & Stillman, B. (1994) · Nature · doi:10.1038/369574a0 · Cited by 1,655
Self-citationRadiation-induced cell cycle arrest compromised by p21 deficiency
Brugarolas, J., Chandrasekaran, C., Gordon, J. I., Beach, D., Jacks, T., & Hannon, G. J. (1995) · Nature · doi:10.1038/377552a0 · Cited by 1,242
Uncoupling of S phase and mitosis induced by anticancer agents in cells lacking p21
Waldman, T., Lengauer, C., Kinzler, K. W., & Vogelstein, B. (1996) · Nature · doi:10.1038/381713a0 · Cited by 728
Cell-cycle inhibition by independent CDK and PCNA binding domains in p21Cip1
Luo, Y., Hurwitz, J., & Massagué, J. (1995) · Nature · doi:10.1038/375159a0 · Cited by 549
Separate domains of p21 involved in the inhibition of Cdk kinase and PCNA
Chen, J., Jackson, P. K., Kirschner, M. W., & Dutta, A. (1995) · Nature · doi:10.1038/374386a0 · Cited by 548
Cyclin-Binding Motifs Are Essential for the Function of p21 CIP1
Chen, J., Saha, P., Kornbluth, S., Dynlacht, B. D., & Dutta, A. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.9.4673 · Cited by 320
Podust, V. N., Podust, L. M., Goubin, F., Ducommun, B., & Huebscher, U. (1995) · Biochemistry · doi:10.1021/bi00027a039 · Cited by 124
Analysis of Wild-Type and Mutant p21 WAF-1 Gene Activities
Lin, J., Reichner, C., Wu, X., & J. Levine, A. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.4.1786 · Cited by 111
Research works printed but not linked: 53
- 10.1091/mbc.3.6.655 · DOI
- Adams, 1996, Identification of a cyclin-cdk2 recognition motif present in substrates and p21-like cyclin-dependent kinase inhibitors., Mol. Cell. Biol., 16, 6623, 10.1128/MCB.16.12.6623 · DOI
- 10.1074/jbc.271.26.15782 · DOI
- Ball, 1996, Cell-cycle arrest and inhibition of cdk4 activity by small peptides basd on the carboxy-terminal domain of p21WAF1., Curr. Biol., 7, 71, 10.1016/S0960-9822(06)00029-7 · DOI
- 10.1101/gad.6.1.71 · DOI
- Boyer, 1996, E7 protein of human papilloma virus-16 induces degradation of retinoblastoma protein through the ubiquitin-proteosome pathway., Cancer Res., 56, 4620
- DeGregori, 1995, Cellular targets for activation by the E2F1 transcription factor include DNA synthesis- and G1/S-regulatory genes., Mol. Cell. Biol., 15, 4215, 10.1128/MCB.15.8.4215 · DOI
- 10.1073/pnas.91.10.4382 · DOI · Paper page
- Demers, 1996, Abrogation of growth arrest signals by human papillomavirus type 16 E7 is mediated by sequences required for transformation., J. Virol., 70, 6862, 10.1128/jvi.70.10.6862-6869.1996 · DOI
- Dimri, 1996, Inhibition of E2F activity by the cyclin-dependent protein kinase inhibitor p21 in cells expressing or lacking a functional retinoblastoma protein., Mol. Cell. Biol., 16, 2987, 10.1128/MCB.16.6.2987 · DOI
- 10.1016/0092-8674(94)90379-4 · DOI · Paper page
- 10.1016/0092-8674(93)90500-P · DOI · Paper page
- 10.1073/pnas.91.18.8655 · DOI · Paper page
- 10.1038/366707a0 · DOI
- 10.1016/S0092-8674(00)81347-1 · DOI
- Halbert, 1992, The E6 and E7 genes of human papillomavirus type 6 have weak immortalizing activity in human epithelial cells., J. Virol., 66, 2125, 10.1128/jvi.66.4.2125-2134.1992 · DOI · Paper page
- 10.1126/science.7863327 · DOI
- 10.1016/0092-8674(93)90499-G · DOI · Paper page
- 10.1091/mbc.6.4.387 · DOI
- Hermeking, 1995, Abrogation of p53-induced cell cycle arrest by c-Myc: Evidence for an inhibitor of p21WAF1/CIP1/SDI1., Oncogene, 11, 1409
- Jones, 1997, Analysis of the p53-mediated G1 growth arrest pathway in cells expressing the human papillomavirus type 16 E7 oncoprotein., J. Virol., 71, 2905, 10.1128/jvi.71.4.2905-2912.1997 · DOI · Paper page
- 10.1073/pnas.93.21.11504 · DOI
- 10.1101/gad.11.7.847 · DOI · Paper page
- 10.1038/371534a0 · DOI
- 10.1016/S0960-9822(02)00452-9 · DOI
- 10.1101/gad.9.8.935 · DOI
- 10.1038/380262a0 · DOI
- 10.1073/pnas.92.12.5451 · DOI
- 10.1038/374131a0 · DOI
- 10.1074/jbc.270.29.17060 · DOI · Paper page
- 10.1006/excr.1994.1063 · DOI · Paper page
- Ohtsubo, 1995, Human cyclin E, a nuclear protein essential for the G1 to S phase transition., Mol. Cell. Biol., 15, 2612, 10.1128/MCB.15.5.2612 · DOI
- 10.1126/science.7863329 · DOI
- 10.1016/0092-8674(90)90188-K · DOI
- 10.1016/0092-8674(88)90493-X · DOI
- Reed, 1996, Cyclin E: In mid-cycle., Biochim. Biophys. Acta, 1287, 151
- 10.1038/382325a0 · DOI
- 10.1101/gad.9.10.1149 · DOI
- 10.1016/S0960-9822(00)00244-X · DOI
- 10.1073/pnas.91.12.5320 · DOI
- Stillman, 1985, Replication and supercoiling of simian virus 40 DNA in cell extracts from human cells., Mol. Cell. Biol., 5, 2051
- 10.1073/pnas.92.22.10187 · DOI
- Tsurimoto, 1991, Replication factors required for SV40 DNA replication in vitro. II. Switching of DNA polymerase α and δ during initiation of leading and lagging strand synthesis., J. Biol. Chem., 266, 1961, 10.1016/S0021-9258(18)52386-3 · DOI
- Waga, 1994, Reconstitution of complete SV40 DNA replication with purified replication factors., J. Biol. Chem., 269, 10923, 10.1016/S0021-9258(17)34146-7 · DOI
- Waldman, 1995, p21 is necessary for the p53-mediated G1 arrest in human cancer cells., Cancer Res., 55, 5187
- 10.1016/S0960-9822(95)00058-3 · DOI
- 10.1038/366701a0 · DOI
- 10.1101/gad.7.8.1572 · DOI
- Xiong, 1996, Alteration of cell cycle kinase complexes in human papillomavirus E6- and E7-expressing fibroblasts precedes neoplastic transformation., J. Virol., 70, 999, 10.1128/jvi.70.2.999-1008.1996 · DOI
- Zerfass, 1995, Sequential activation of cyclin E and cyclin A gene expression by human papillomavirus type 16 E7 through sequences necessary for transformation., J. Virol., 69, 6389, 10.1128/jvi.69.10.6389-6399.1995 · DOI · Paper page
- Zerfass-Thome, 1996, Inactivation of the cdk inhibitor p27KIP1 by the human papillomavirus type 16 E7 oncoprotein., Oncogene, 13, 2323
- 10.1101/gad.8.15.1750 · DOI
- zur Hausen, 1996, Papillomavirus infections—A major cause of human cancers., Biochim. Biophys. Acta, 1288, F55
Cited by
CDK inhibitors: Cell cycle regulators and beyond
Besson, A., Dowdy, S. F., & Roberts, J. M. (2008) · Developmental Cell · doi:10.1016/j.devcel.2008.01.013 · Cited by 1,152
Molecular biology of human papillomavirus infection and cervical cancer
Doorbar, J. (2006) · Clinical Science · doi:10.1042/cs20050369 · Cited by 1,072
Narisawa‐Saito, M., & Kiyono, T. (2007) · Cancer Science · doi:10.1111/j.1349-7006.2007.00546.x · Cited by 528
Thomas, D. M., Carty, S. A., Piscopo, D. M., Lee, J.-S., Wang, W.-F., Forrester, W. C., & Hinds, P. W. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00327-6 · Cited by 361
Zhen, S., Hua, L., Takahashi, Y., Narita, S., Liu, Y.-H., & Li, Y. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.07.014 · Cited by 219
Metadata
- Authors
- Funk, J. O., Waga, S., Harry, J. B., Espling, E., Stillman, B., & Galloway, D. A.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1997-08-15
- Volume
- 11
- Issue
- 16
- Pages
- 2090-2100
- ISSN
- 0890-9369
- 1549-5477
- Cited by
- 419
- References
- 9
- Language
- en
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- Funk, J. O., Waga, S., Harry, J. B., Espling, E., Stillman, B., & Galloway, D. A. (1997). Inhibition of CDK activity and PCNA-dependent DNA replication by p21 is blocked by interaction with the HPV-16 E7 oncoprotein. Genes & Development. https://doi.org/10.1101/gad.11.16.2090
