Abstract
Melanoma is one of the most aggressive skin cancers with fiercely increasing incidence and mortality. Since the progressive understanding of the mutational landscape and immunologic pathogenic factors in melanoma, the targeted therapy and immunotherapy have been recently established and gained unprecedented improvements for melanoma treatment. However, the prognosis of melanoma patients remains unoptimistic mainly due to the resistance and nonresponse to current available drugs. Ubiquitination is a posttranslational modification which plays crucial roles in diverse cellular biological activities and participates in the pathogenesis of various cancers, including melanoma. Through the regulation of multiple tumor promoters and suppressors, ubiquitination is emerging as the key contributor and therefore a potential therapeutic target for melanoma. Herein, we summarize the current understanding of ubiquitination in melanoma, from mechanistic insights to clinical progress, and discuss the prospect of ubiquitination modification in melanoma treatment.
Highlights
Melanoma is among the most aggressive cancers arising from the malignant transformation of melanocytes [1]
NF-κB is constitutively activated at high levels in melanoma cells compared with melanocytes, which results from the dysregulated ubiquitination. β-Trcp is the main E3 ubiquitin ligase that facilitates IκB ubiquitination and subsequent NF-κ B activation [81]
The ubiquitination of RIP1 was prominently increased in melanoma cells, which was responsible for the high expression of RIP1 and constitutive activation of NF-κB
Summary
Melanoma is among the most aggressive cancers arising from the malignant transformation of melanocytes [1]. In addition to the already known driver mutations, the genetic variations of ubiquitination-related enzymes uncovered by high-throughput sequencing are greatly implicated in melanoma tumorigenesis, with BRCA1-a ssociated protein-1 (BAP1), F-box and WD repeat domain-containing 7 (FBXW7) and PARK2 as the best representations. NF-κB is constitutively activated at high levels in melanoma cells compared with melanocytes, which results from the dysregulated ubiquitination.
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