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E2-EPF UCP regulates stability and functions of missense mutant pVHL via ubiquitin mediated proteolysis

Overview of attention for article published in BMC Cancer, October 2015
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Title
E2-EPF UCP regulates stability and functions of missense mutant pVHL via ubiquitin mediated proteolysis
Published in
BMC Cancer, October 2015
DOI 10.1186/s12885-015-1786-8
Pubmed ID
Authors

Kyeong-Su Park, Ju Hee Kim, Hee Won Shin, Kyung-Sook Chung, Dong-Soo Im, Jung Hwa Lim, Cho-Rok Jung

Abstract

Missense mutation of VHL gene is frequently detected in type 2 VHL diseases and linked to a wide range of pVHL functions and stability. Certain mutant pVHLs retain ability to regulate HIFs but lose their function by instability. In this case, regulating of degradation of mutant pVHLs, can be postulated as therapeutic method. The stability and cellular function of missense mutant pVHLs were determine in HEK293T transient expressing cell and 786-O stable cell line. Ubiquitination assay of mutant VHL proteins was performed in vitro system. Anticacner effect of adenovirus mediated shUCP expressing was evaluated using ex vivo mouse xenograft assay. Three VHL missense mutants (V155A, L158Q, and Q164R) are directly ubiquitinated by E2-EPF UCP (UCP) in vitro. Mutant pVHLs are more unstable than wild type in cell. Missense mutant pVHLs interact with UCP directly in both in vitro and cellular systems. Lacking all of lysine residues of pVHL result in resistance to ubiquitination thereby increase its stability. Missense mutant pVHLs maintained the function of E3 ligase to ubiquitinate HIF-1α in vitro. In cells expressing mutant pVHLs, Glut-1 and VEGF were relatively upregulated compared to their levels in cells expressing wild-type. Depletion of UCP restored missense mutant pVHLs levels and inhibited cell growth. Adenovirus-mediated shUCP RNA delivery inhibited tumor growth in ex vivo mouse xenograft model. These data suggest that targeting of UCP can be one of therapeutic method in type 2 VHL disease caused by unstable but functional missense mutant pVHL.

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Mendeley readers

The data shown below were compiled from readership statistics for 11 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 11 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 4 36%
Student > Bachelor 4 36%
Student > Ph. D. Student 3 27%
Readers by discipline Count As %
Agricultural and Biological Sciences 6 55%
Biochemistry, Genetics and Molecular Biology 2 18%
Medicine and Dentistry 2 18%
Nursing and Health Professions 1 9%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 28 October 2015.
All research outputs
#5,544,791
of 6,500,718 outputs
Outputs from BMC Cancer
#2,434
of 3,083 outputs
Outputs of similar age
#164,946
of 207,323 outputs
Outputs of similar age from BMC Cancer
#163
of 218 outputs
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