Imperial College London
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Professor Vasso Episkopou

Faculty of Medicine, Department of Brain Sciences

Emeritus Professor
 
 
 
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Contact

 

+44 (0)20 7594 6587vasso.episkopou

 
 
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Location

 

Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Birkou:2022:10.3389/fmolb.2022.844129,
author = {Birkou, M and Raptis, V and Marousis, KD and Tsevis, A and Bourikas, K and Bentrop, D and Episkopou, V and Spyroulias, GA},
doi = {10.3389/fmolb.2022.844129},
journal = {Frontiers in Molecular Biosciences},
title = {Impact of a single nucleotide polymorphism on the 3D protein structure and ubiquitination activity of E3 ubiquitin ligase arkadia},
url = {http://dx.doi.org/10.3389/fmolb.2022.844129},
volume = {9},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Single nucleotide polymorphisms (SNPs) are genetic variations which can play a vital role in the study of human health. SNP studies are often used to identify point mutations that are associated with diseases. Arkadia (RNF111) is an E3 ubiquitin ligase that enhances transforming growth factor-beta (TGF-β) signaling by targeting negative regulators for degradation. Dysregulation of the TGF-β pathway is implicated in cancer because it exhibits tumor suppressive activity in normal cells while in tumor cells it promotes invasiveness and metastasis. Τhe SNP CGT > TGT generated an amino-acid (aa) substitution of Arginine 957 to Cysteine on the enzymatic RING domain of Arkadia. This was more prevalent in a tumor than in a normal tissue sample of a patient with colorectal cancer. This prompted us to investigate the effect of this mutation in the structure and activity of Arkadia RING. We used nuclear magnetic resonance (NMR) to analyze at an atomic-level the structural and dynamic properties of the R957C Arkadia RING domain, while ubiquitination and luciferase assays provided information about its enzymatic functionality. Our study showed that the R957C mutation changed the electrostatic properties of the RING domain however, without significant effects on the structure of its core region. However, the functional studies revealed that the R957C Arkadia exhibits significantly increased enzymatic activity supporting literature data that Arkadia within tumor cells promotes aggressive and metastatic behavior.
AU  - Birkou,M
AU  - Raptis,V
AU  - Marousis,KD
AU  - Tsevis,A
AU  - Bourikas,K
AU  - Bentrop,D
AU  - Episkopou,V
AU  - Spyroulias,GA
DO  - 10.3389/fmolb.2022.844129
PY  - 2022///
SN  - 2296-889X
TI  - Impact of a single nucleotide polymorphism on the 3D protein structure and ubiquitination activity of E3 ubiquitin ligase arkadia
T2  - Frontiers in Molecular Biosciences
UR  - http://dx.doi.org/10.3389/fmolb.2022.844129
UR  - https://www.frontiersin.org/articles/10.3389/fmolb.2022.844129/full
UR  - http://hdl.handle.net/10044/1/95844
VL  - 9
ER  -
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