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DOI | 10.1038/s41467-018-05705-4 |
Usp9x regulates Ets-1 ubiquitination and stability to control NRAS expression and tumorigenicity in melanoma | |
Potu, Harish1,2; Peterson, Luke F.1,2; Kandarpa, Malathi1,2; Pal, Anupama1,2; Sun, Hanshi3; Durham, Alison4; Harms, Paul W.4,5; Hollenhorst, Peter C.6; Eskiocak, Ugur7,8,10; Talpaz, Moshe1,2; Donato, Nicholas J.9 | |
2017-02-15 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2017 |
卷号 | 8 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | ETS transcription factors are commonly deregulated in cancer by chromosomal translocation, overexpression or post-translational modification to induce gene expression programs essential in tumorigenicity. Targeted destruction of these proteins may have therapeutic impact. Here we report that Ets-1 destruction is regulated by the deubiquitinating enzyme, Usp9x, and has major impact on the tumorigenic program of metastatic melanoma. Ets-1 deubiquitination blocks its proteasomal destruction and enhances tumorigenicity, which could be reversed by Usp9x knockdown or inhibition. Usp9x and Ets-1 levels are coincidently elevated in melanoma with highest levels detected in metastatic tumours versus normal skin or benign skin lesions. Notably, Ets-1 is induced by BRAF or MEK kinase inhibition, resulting in increased NRAS expression, which could be blocked by inactivation of Usp9x and therapeutic combination of Usp9x and MEK inhibitor fully suppressed melanoma growth. Thus, Usp9x modulates the Ets-1/NRAS regulatory network and may have biologic and therapeutic implications |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000394222100001 |
WOS关键词 | TERT PROMOTER MUTATIONS ; TRANSCRIPTION FACTOR ; DEUBIQUITINASE INHIBITION ; FEEDBACK INHIBITION ; PROTEASOME SYSTEM ; MOLECULAR-BIOLOGY ; POOR-PROGNOSIS ; ONCOGENIC NRAS ; RAS ; CANCER |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203939 |
专题 | 资源环境科学 |
作者单位 | 1.Univ Michigan, Sch Med, Dept Internal Med, Div Hematol Oncol, Ann Arbor, MI 48109 USA; 2.Ctr Comprehens Canc, Ann Arbor, MI 48109 USA; 3.Univ Michigan, Sch Dent, Dept Periodont & Oral Med, Ann Arbor, MI 48109 USA; 4.Univ Michigan, Sch Med, Dept Dermatol, Ann Arbor, MI 48109 USA; 5.Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA; 6.Indiana Univ Bloomington, Med Sci Program, Dept Biochem & Mol Biol, 1001 Third St, Bloomington, IN 47405 USA; 7.Univ Texas Southwestern Med Ctr Dallas, Childrens Res Inst, Dallas, TX 75390 USA; 8.Univ Texas Southwestern Med Ctr Dallas, Howard Hughes Med Inst, Dept Pediat, Dallas, TX 75390 USA; 9.Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA; 10.Compass Therapeut, 450 Kendall St, Cambridge, MA 02142 USA |
推荐引用方式 GB/T 7714 | Potu, Harish,Peterson, Luke F.,Kandarpa, Malathi,et al. Usp9x regulates Ets-1 ubiquitination and stability to control NRAS expression and tumorigenicity in melanoma[J]. NATURE COMMUNICATIONS,2017,8. |
APA | Potu, Harish.,Peterson, Luke F..,Kandarpa, Malathi.,Pal, Anupama.,Sun, Hanshi.,...&Donato, Nicholas J..(2017).Usp9x regulates Ets-1 ubiquitination and stability to control NRAS expression and tumorigenicity in melanoma.NATURE COMMUNICATIONS,8. |
MLA | Potu, Harish,et al."Usp9x regulates Ets-1 ubiquitination and stability to control NRAS expression and tumorigenicity in melanoma".NATURE COMMUNICATIONS 8(2017). |
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