Do VHL and HIF-1 mirror p53 and Mdm-2? Degradation-transactivation loops of oncoproteins and tumor suppressors (original) (raw)

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• Published: 12 March 2001

Oncogene volume 20, pages 395–398 (2001)Cite this article

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Abstract

Recently it has been shown that the VHL tumor suppressor targets the hypoxia-inducible transcription factor (HIF-1) for ubiquitin-dependent degradation by the proteasome. Past mysteries of the p53 tumor suppressor help to solve the present puzzles of the VHL tumor suppressor. Thus, Mdm-2 targets the p53 tumor suppressor for ubiquitin-dependent degradation by the proteasome, but, in addition, the p53 transcription factor induces Mdm-2, thus, establishing a feedback loop. Hypoxia or DNA damage by abrogating binding of HIF-1 with VHL and p53 with Mdm-2, respectively, leads to stabilization and accumulation transcriptionally active HIF-1 and p53. More detailed analysis depicts the VHL/HIF-1 pair as the p53/mdm-2 pair that is turned upside down, suggesting that VHL may be a HIF-1-inducible gene of the feedback loop. The extended model proposes that an oncoprotein and a tumor suppressor due to transactivation coupled with feedback protein degradation might form functional pairs (Rb/E7, E2F/Rb, E2F/Mdm-2, catenin/APC, p27, cyclin D1, Rb/gankyrin), thus, predicting missing links.

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1. Medicine Branch, National Cancer Institute, NIH, Bethesda, 20892, Maryland, MD, USA
   Mikhail V Blagosklonny

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1. Mikhail V Blagosklonny
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Blagosklonny, M. Do VHL and HIF-1 mirror p53 and Mdm-2? Degradation-transactivation loops of oncoproteins and tumor suppressors.Oncogene 20, 395–398 (2001). https://doi.org/10.1038/sj.onc.1204055

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• Received: 26 June 2000
• Revised: 23 October 2000
• Accepted: 23 October 2000
• Published: 12 March 2001
• Issue Date: 18 January 2001
• DOI: https://doi.org/10.1038/sj.onc.1204055

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