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Updated: Feb 8, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
A Cu2+ complex induces the aggregation of human papillomavirus oncoprotein E6 and stabilizes p53
Amit Kumar1,2,3, Lars T Kuhn1, Jochen Balbach2,3
1Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, University of Leeds, UK.
Abstract:
Papillomavirus oncoprotein E6 is a critical factor in the modulation of cervical cancer in humans. At the molecular level, formation of the E6-E6AP-p53 ternary complex, which directs p53's degradation, is the key instigator of cancer transforming properties. Herein, a Cu2+ anthracenyl-terpyridine complex is described which specifically induces the aggregation of E6 in vitro and in cultured cells. For a hijacking mechanism, both E6 and E6AP are required for p53 ubiquitination and degradation. The Cu2+ complex interacts with E6 at the E6AP and p53 binding sites. We show that E6 function is suppressed by aggregation, rendering it incapable of hijacking p53 and thus increasing its cellular level. Therapeutic treatments of cervical cancer are currently unavailable to infected individuals. We anticipate that this Cu2+ complex might open up a new therapeutic avenue for the design and development of new chemical entities for the diagnosis and treatment of HPV-induced cancers.
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