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Cloning of cDNAs for cellular proteins that bind to the retinoblastoma gene product
Abstract
The E7 transforming protein of human papilloma virus-16 binds to the retinoblastoma gene product (pRb) through a nine-amino-acid segment of E7 (21-29). This segment of E7 is homologous to the pRb-binding domains of the simian virus 40 large T and adenovirus E1A transforming proteins. Each of these viral transforming proteins bind to the same region of pRb. To isolate cellular proteins that interact with this viral protein-binding domain on pRb, we used recombinant pRb to screen a human complementary DNA expression library. Two cDNAs were isolated that encode retinoblastoma binding proteins (RBP-1 and RBP-2). We report here that these RBP genes exist in separate loci and produce discrete messenger RNAs. The predicted amino-acid sequence of these genes showed no homology to known proteins, but both RBPs contain the pRb binding motif conserved between E7, large T and E1A14. In vitro expression of the RBP cDNAs yielded proteins that specifically bound to pRb. Recombinant E7 protein, the E7 21-29 peptide and the homologous RBP-1 peptide inhibited RBP-pRb binding. Mutations introduced into the putative pRb-binding segment in RBP-1 impaired its binding activity. These studies indicate that the cellular RBP-1, RBP-2 and viral E7 proteins interact with pRb through similar domains.
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“HPV oncoproteins do not have intrinsic enzymatic activity and nor do they share extensive sequence similarity with any host proteins [116,117], but they are able to interact with and modulate many host cell proteins to contribute to all the cancer cell hallmarks”
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 [117]
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A Chromatin-Mediated Reversible Drug-Tolerant State in Cancer Cell Subpopulations
Sharma, S. V., Lee, D. Y., Li, B., Quinlan, M. P., Takahashi, F., Maheswaran, S., McDermott, U., Azizian, N., Zou, L., Fischbach, M. A., et al. (2010) · Cell · doi:10.1016/j.cell.2010.02.027 · Cited by 2,770
JmjC-domain-containing proteins and histone demethylation
Klose, R. J., Kallin, E. M., & Zhang, Y. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1945 · Cited by 1,290
Retinoblastoma protein partners
(2001) · Advances in Cancer Research · doi:10.1016/s0065-230x(01)82001-7 · Cited by 349
Chang, S., Yim, S., & Park, H. (2019) · Experimental & Molecular Medicine · doi:10.1038/s12276-019-0230-6 · Cited by 228
Kaelin, W. G. (2011) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2011.76.010975 · Cited by 161
Metadata
- Authors
- Defeo-Jones, D., Huang, P. S., Jones, R. E., Haskell, K. M., Vuocolo, G. A., Hanobik, M. G., Huber, H. E., & Oliff, A.
- Venue
- Nature
- Published
- 1991-07
- Volume
- 352
- Issue
- 6332
- Pages
- 251-254
- ISSN
- 0028-0836
- 1476-4687
- Cited by
- 263
- References
- 2
- Language
- en
- Licence
- www.springer.com/tdm (tdm)
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- Defeo-Jones, D., Huang, P. S., Jones, R. E., Haskell, K. M., Vuocolo, G. A., Hanobik, M. G., Huber, H. E., & Oliff, A. (1991). Cloning of cDNAs for cellular proteins that bind to the retinoblastoma gene product. Nature. https://doi.org/10.1038/352251a0