Abstract
Most human cancers show perturbation of growth regulation mediated by the tumour-suppressor proteins retinoblastoma (RB) and p53 (ref. 1), indicating that loss of both pathways is necessary for tumour development. Loss of RB function leads to abnormal proliferation related to the deregulation of the E2F transcription factors, but also results in the activation of p53, which suppresses cell growth. Here we show that E2F-1 directly activates expression of the human tumour-suppressor protein p14ARF (the mouse homologue is called p19ARF), which binds to the MDM2-p53 complex and prevents p53 degradation2,5. These results complete a pathway linking abnormal proliferative signals, such as loss of RB, with the activation of a p53 response, through E2F-1 and p14ARF. They suggest that E2F-1, a protein inherently activated by cell-cycle progression, is part of a fail-safe mechanism to protect against aberrant cell growth.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Palmero, I. & Peters, G. Cancer Surv. 27, 351–367 (1996).
Pomerantz, J.et al. Cell 92, 713–723 (1998).
Zhang, Y., Xiong, Y. & Yarbrough, W. G. Cell 92, 725–734 (1998).
Stott, F. et al. EMBO J. (in the press).
Kamijo, T.et al. Proc. Natl Acad. Sci. USA 95, 8292–8297 (1998).
Phillips, A. C., Bates, S., Ryan, K. M., Helin, K. & Vousden, K. H. Genes Dev. 11, 1853–1863 (1997).
Lukas, J., Petersen, B. O., Holm, K., Bartek, J. & Helin, K. Mol. Cell. Biol. 16, 1047–1057 (1996).
Kamijo, T.et al. Cell 91, 649–659 (1997).
Morgenbesser, S. D., Williams, B. O., Jacks, T. & DePinho, R. A. Nature 371, 72–74 (1994).
Lowe, S. W. & Ruley, H. E. Genes Dev. 7, 535–545 (1993).
Hermeking, H. & Eick, D. Science 265, 2091–2092 (1994).
Kowalik, T. F., DeGregori, J., Leone, G., Jakoi, L. & Nevins, J. R. Cell Growth Differ. 9, 113–118 (1998).
Author information
Authors and Affiliations
Supplementary Information
Rights and permissions
About this article
Cite this article
Bates, S., Phillips, A., Clark, P. et al. p14ARF links the tumour suppressors RB and p53. Nature 395, 124–125 (1998). https://doi.org/10.1038/25867
Issue Date:
DOI: https://doi.org/10.1038/25867
This article is cited by
-
High expression of CDKN2A is associated with poor prognosis in colorectal cancer and may guide PD-1-mediated immunotherapy
BMC Cancer (2023)
-
CRL2-KLHDC3 E3 ubiquitin ligase complex suppresses ferroptosis through promoting p14ARF degradation
Cell Death & Differentiation (2022)
-
MYC: a multipurpose oncogene with prognostic and therapeutic implications in blood malignancies
Journal of Hematology & Oncology (2021)
-
Tumor-associated antigen Prame targets tumor suppressor p14/ARF for degradation as the receptor protein of CRL2Prame complex
Cell Death & Differentiation (2021)
-
Expression of p53 is significantly associated with recurrence-free survival and overall survival in pleuropulmonary blastoma (PPB): a report from the International Pleuropulmonary Blastoma/DICER1 Registry
Modern Pathology (2021)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.