E3 ubiquitin ligases as drug targets and prognostic biomarkers in melanoma

Medicina
Kristina BielskienėErnestas Janulionis

Abstract

Melanomas are highly proliferative and invasive, and are most frequently metastatic. Despite many advances in cancer treatment over the last several decades, the prognosis for patients with advanced melanoma remains poor. New treatment methods and strategies are necessary. 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 tum...Continue Reading

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