E3 ubiquitin ligases as drug targets and prognostic biomarkers in melanoma
The main hallmark of cancer is uncontrolled cellular proliferation with alterations in the expression of proteins. Ubiquitin and ubiquitin-related proteins posttranslationally modify proteins and thereby alter their functions. The ubiquitination process is involved in various physiological responses, including cell growth, cell death, and DNA damage repair. E3 ligases, the most specific enzymes of ubiquitination system, participate in the turnover of many key regulatory proteins and in the development of cancer.
E3 ligases are of interest as drug targets for their ability to regulate proteins stability and functions. Compared to the general proteasome inhibitor bortezomib, which blocks the entire protein degradation, drugs that target a particular E3 ligase are expected to have better selectivity with less associated toxicity. Components of different E3 ligases complexes (FBW7, MDM2, RBX1/ROC1, RBX2/ROC2, cullins and many others) are known as oncogenes or tumor suppressors in melanomagenesis. These proteins participate in regulation of different cellular pathways and such important proteins in cancer development as p53 and Notch. In this review we summarized published data on the role of known E3 ligases in the development of melanoma and discuss the inhibitors of E3 ligases as a novel approach for the treatment of malignant melanomas.
Bielskienė, K.; Bagdonienė, L.; Mozūraitienė, J.; Kazbarienė, B.; Janulionis, E. E3 ubiquitin ligases as drug targets and prognostic biomarkers in melanoma. Medicina 2015, 51, 1-9.
Bielskienė K, Bagdonienė L, Mozūraitienė J, Kazbarienė B, Janulionis E. E3 ubiquitin ligases as drug targets and prognostic biomarkers in melanoma. Medicina. 2015; 51(1):1-9.Chicago/Turabian Style
Bielskienė, Kristina; Bagdonienė, Lida; Mozūraitienė, Julija; Kazbarienė, Birutė; Janulionis, Ernestas. 2015. "E3 ubiquitin ligases as drug targets and prognostic biomarkers in melanoma." Medicina 51, no. 1: 1-9.