oncogenic activity
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Author(s):  
Mirella Belleri ◽  
Paola Chiodelli ◽  
Marzia Corli ◽  
Miriam Capra ◽  
Marco Presta

Engineering ◽  
2021 ◽  
Author(s):  
Tao Rui ◽  
Xueyou Zhang ◽  
Shi Feng ◽  
Haitao Huang ◽  
Shaowei Zhan ◽  
...  

2021 ◽  
Author(s):  
Ian McCabe ◽  
Huanqing Zhang ◽  
Jonathan A. Cooper ◽  
David L. Turner ◽  
Anne B. Vojtek

Membrane localization of Ras proteins is necessary for their biological functions and oncogenic activity. We report here on the identification of Brain I3 Binding Protein (BRI3BP) as a novel binding partner for Ras. We show that K-Ras4B plasma membrane localization and biological function are reduced in the absence of BRI3BP. BRI3BP interacts with K-Ras4B and K-Ras4A and our data suggest that BRI3BP operates within the recycling endosomal compartment to regulate K-Ras localization to the plasma membrane. This study uncovers a new regulatory protein for Ras membrane localization.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Urna Kansakar ◽  
Wei Wang ◽  
Vesna Markovic ◽  
Khalid Sossey‑Alaoui

2021 ◽  
Author(s):  
Gerard L. Brien ◽  
Raul Bardini Bressan ◽  
Craig Monger ◽  
Dáire Gannon ◽  
Eimear Lagan ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Marita Zoma ◽  
Laura Curti ◽  
Dheeraj Shinde ◽  
Domenico Albino ◽  
Abhishek Mitra ◽  
...  

AbstractThe TMPRSS2-ERG gene fusion is the most frequent alteration observed in human prostate cancer. However, its role in disease progression is still unclear. In this study, we uncover an important mechanism promoting ERG oncogenic activity. We show that ERG is methylated by Enhancer of zest homolog 2 (EZH2) at a specific lysine residue (K362) located within the internal auto-inhibitory domain. Mechanistically, K362 methylation modifies intra-domain interactions, favors DNA binding and enhances ERG transcriptional activity. In a genetically engineered mouse model of ERG fusion-positive prostate cancer (Pb-Cre4 Ptenflox/floxRosa26-ERG, ERG/PTEN), ERG K362 methylation is associated with PTEN loss and progression to invasive adenocarcinomas. In both ERG positive VCaP cells and ERG/PTEN mice, PTEN loss results in AKT activation and EZH2 phosphorylation at serine 21 that favors ERG methylation. We find that ERG and EZH2 interact and co-occupy several sites in the genome forming trans-activating complexes. Consistently, ERG/EZH2 co-regulated target genes are deregulated preferentially in tumors with concomitant ERG gain and PTEN loss and in castration-resistant prostate cancers. Collectively, these findings identify ERG methylation as a post-translational modification sustaining disease progression in ERG-positive prostate cancers.


2021 ◽  
Author(s):  
Li-Ting Wang ◽  
Kwei-Yan Liu ◽  
Shyh-Shin Chiou ◽  
Shau-Ku Huang ◽  
Shih-Hsien Hsu ◽  
...  
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