Ubiquitin–proteasome system-targeted therapy for uveal melanoma: what is the evidence? |
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作者姓名: | Chen-xi Zhao Chen-ming Zeng Ke Wang Qiao-jun He Bo Yang Fan-fan Zhou Hong Zhu |
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作者单位: | Zhejiang Province Key Laboratory of Anti-Cancer Drug Research;NHC Key Laboratory of Nuclear Medicine;Sydney Pharmacy School |
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基金项目: | supported by the National Natural Science Foundation of China(81973349 to HZ);the Young Talent's Subsidy Project in Science and Education of the Department of Public Health of Jiangsu Province(QNRC2016627 to KW);the Six Talent Peaks Project in Jiangsu Province(WSW-047 to KW). |
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摘 要: | Uveal melanoma(UM)is a rare ocular tumor.The loss of BRCA1-associated protein 1(BAP1)and the aberrant activation of G protein subunit alpha q(GNAQ)/G protein subunit alpha 11(GNA11)contribute to the frequent metastasis of UM.Thus far,limited molecular-targeted therapies have been developed for the clinical treatment of UM.However,an increasing number of studies have revealed the close relationship between the ubiquitin proteasome system(UPS)and the malignancy of UM.UPS consists of a three-enzyme cascade,i.e.ubiquitin-activating enzymes(E1s);ubiquitin-conjugating enzymes(E2s);and ubiquitin-protein ligases(E3s),as well as 26S proteasome and deubiquitinases(DUBs),which work coordinately to dictate the fate of intracellular proteins through regulating ubiquitination,thus influencing cell viability.Due to the critical role of UPS in tumors,we here provide an overview of the crosstalk between UPS and the malignancy of UM,discuss the current UPS-targeted therapies in UM and highlight its potential in developing novel regimens for UM.
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关 键 词: | Uveal melanoma BAP1 ubiquitin-proteasome system DUB molecular targeted therapy |
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