Regulation of MITF stability by the USP13 deubiquitinase

Zhao, Xinzhen; Fiske, Brian P.; Kawakami, Akinori; Li, Juying; Fisher, David E.

doi:10.1038/ncomms1421

Cited by 86 publications

(95 citation statements)

References 35 publications

(57 reference statements)

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“…USPs represent the largest family of ubiquitin‐deconjugating enzymes. To date, the first well‐studied USP in melanoma was USP13, of which the significant up‐regulation contributed to melanoma growth via deubiquitination and stabilization of melanocyte lineage‐specific transcriptional factor MITF 13. Apart from this, USP8 and USP15 have been reported to act as oncogenic factor in melanoma, highlighting that both ubiquitin‐conjugating and ubiquitin‐deconjugating enzymes played important roles in melanoma tumour biology 31, 32.…”

Section: Discussionmentioning

confidence: 99%

“…For melanoma, the mutations of ubiquitination‐related genes such as BRCA1‐associated protein‐1(BAP1), F‐boxand WD repeat domain‐containing 7 (FBXW7) and PARK2 are frequently identified and participated in melanoma tumourigenesis 11. What is more, the activation of some critical signalling pathways in melanoma development including NF‐κB and MITF are also subtly regulated by ubiquitination,12, 13 demonstrating its vital pathogenic role in melanoma. Notably, previous studies mainly focused on the regulatory role of ubiquitin‐conjugating enzymes, especially E3 ubiquitin ligases in melanoma.…”

Section: Introductionmentioning

confidence: 99%

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Up‐regulated deubiquitinase USP4 plays an oncogenic role in melanoma

Guo

Pei

et al. 2018

J Cellular Molecular Medi

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Melanoma is the most malignant skin cancer with increasing incidence worldwide. Although innovative therapies such as BRAF inhibitor and immune checkpoint inhibitor have gained remarkable advances, metastatic melanoma remains an incurable disease for its notorious aggressiveness. Therefore, further clarification of the underlying mechanism of melanoma pathogenesis is critical for the improvement of melanoma therapy. Ubiquitination is an important regulatory event for cancer hallmarks and melanoma development, and the deubiquitinating enzymes including ubiquitin‐specific peptidase (USP) families are greatly implicated in modulating cancer biology. Herein, we first found that the expression of the deubiquitinase USP4 was significantly up‐regulated in melanoma tissues and cell lines. Furthermore, although USP4 knockdown had little impact on melanoma cell proliferation, it could increase the sensitivity to DNA damage agent cisplatin. We subsequently showed that USP4 regulated cisplatin‐induced cell apoptosis via p53 signalling. More importantly, USP4 could accentuate the invasive and migratory capacity of melanoma cells by promoting epithelial‐mesenchymal transition. Altogether, our results demonstrate that the up‐regulated USP4 plays an oncogenic role in melanoma by simultaneously suppressing stress‐induced cell apoptosis and facilitating tumour metastasis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Up‐regulated deubiquitinase USP4 plays an oncogenic role in melanoma

Guo

Pei

et al. 2018

J Cellular Molecular Medi

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“…For example, USP13 appears to be responsible for the protein stability of microphthalmia-associated transcription factor, which is essential for melanocyte development (37). USP13 can reduce the ubiquitination and degradation of Sky2, the F-box adaptor of the E3 ubiquitin ligase SCF Skp2 (47).…”

Section: Discussionmentioning

confidence: 99%

Ubiquitin-Specific Protease 13 Regulates IFN Signaling by Stabilizing STAT1

Yeh

Yang

et al. 2013

The Journal of Immunology

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The IFN immune system comprises type I, II, and III IFNs, signals through the JAK-STAT pathway, and plays central roles in host defense against viral infection. Posttranslational modifications such as ubiquitination regulate diverse molecules in the IFN pathway. To search for the deubiquitinating enzymes (DUBs) involved in the antiviral activity of IFN, we used RNA interference screening to identify a human DUB, ubiquitin-specific protease (USP) 13, whose expression modulates the antiviral activity of IFN-α against dengue virus serotype 2 (DEN-2). The signaling events and anti–DEN-2 activities of IFN-α and IFN-γ were reduced in cells with USP13 knockdown but enhanced with USP13 overexpression. USP13 may regulate STAT1 protein because the protein level and stability of STAT1 were increased with USP13 overexpression. Furthermore, STAT1 ubiquitination was reduced in cells with USP13 overexpression and increased with USP13 knockdown regardless of with or without IFN-α treatment. Thus, USP13 positively regulates type I and type II IFN signaling by deubiquitinating and stabilizing STAT1 protein. Overall, to our knowledge, USP13 is the first DUB identified to modulate STAT1 and play a role in the antiviral activity of IFN against DEN-2 replication.

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“…One biochemical consequence of MAPK pathway activation is the direct phosphorylation of MITF by ERK/MAPK on Ser 73, an effect that was shown to enhance molecular recruitment of the coactivator p300 to MITF Price et al 1998). Another consequence of this MITF phosphorylation is ubiquitination and proteolysis of MITF (Wu et al 2000;Xu et al 2000), an effect recently shown to be antagonized by the deubiquitinase USP13 (Zhao et al 2011). Of note, bacterial artificial chromosomes containing Ser 73-to-alanine mutation of MITF were capable of rescuing coat color/pigmentation of Mitfdeficient mice ).…”

Section: Mitf-melanocyte Master Regulatormentioning

confidence: 99%

Melanoma: from mutations to medicine

et al. 2012

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Melanoma is often considered one of the most aggressive and treatment-resistant human cancers. It is a disease that, due to the presence of melanin pigment, was accurately diagnosed earlier than most other malignancies and that has been subjected to countless therapeutic strategies. Aside from early surgical resection, no therapeutic modality has been found to afford a high likelihood of curative outcome. However, discoveries reported in recent years have revealed a near avalanche of breakthroughs in the melanoma field—breakthroughs that span fundamental understanding of the molecular basis of the disease all the way to new therapeutic strategies that produce unquestionable clinical benefit. These discoveries have been born from the successful fruits of numerous researchers working in many—sometimes-related, although also distinct—biomedical disciplines. Discoveries of frequent mutations involving BRAF(V600E), developmental and oncogenic roles for the microphthalmia-associated transcription factor (MITF) pathway, clinical efficacy of BRAF-targeted small molecules, and emerging mechanisms underlying resistance to targeted therapeutics represent just a sample of the findings that have created a striking inflection in the quest for clinically meaningful progress in the melanoma field.

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Regulation of MITF stability by the USP13 deubiquitinase

Cited by 86 publications

References 35 publications

Up‐regulated deubiquitinase USP4 plays an oncogenic role in melanoma

Up‐regulated deubiquitinase USP4 plays an oncogenic role in melanoma

Ubiquitin-Specific Protease 13 Regulates IFN Signaling by Stabilizing STAT1

Melanoma: from mutations to medicine

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