Ubiquitin-specific protease 28 is overexpressed in human glioblastomas and contributes to glioma tumorigenicity by regulating MYC expression

Wang, Zengwu; Song, Qimin; Xue, Jian; Zhao, Yumei; Qin, Shiqiang

doi:10.1177/1535370215595468

Cited by 22 publications

(14 citation statements)

References 21 publications

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“…USP13 was found preferentially expressed in GSCs while SCF FBXL14 was predominantly expressed in non-stem glioma cells, enabling preferential stabilization of c-Myc in GSCs. USP28 was previously shown to stabilize c-Myc in HeLa and U2OS cells by antagonizing SCF FBW7a -mediated degradation and a more recent study has now reported its overexpression in GBM (269,313). It has also been demonstrated that high expression of TRIP13, which stabilized c-Myc by inhibiting FBW7 transcription, correlates with poor patient survival (203).…”

Section: Stem Cell Maintenancementioning

confidence: 98%

Targeting the Ubiquitin System in Glioblastoma

et al. 2020

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Glioblastoma is the most common primary brain tumor in adults with poor overall outcome and 5-year survival of less than 5%. Treatment has not changed much in the last decade or so, with surgical resection and radio/chemotherapy being the main options. Glioblastoma is highly heterogeneous and frequently becomes treatment-resistant due to the ability of glioblastoma cells to adopt stem cell states facilitating tumor recurrence. Therefore, there is an urgent need for novel therapeutic strategies. The ubiquitin system, in particular E3 ubiquitin ligases and deubiquitinating enzymes, have emerged as a promising source of novel drug targets. In addition to conventional small molecule drug discovery approaches aimed at modulating enzyme activity, several new and exciting strategies are also being explored. Among these, PROteolysis TArgeting Chimeras (PROTACs) aim to harness the endogenous protein turnover machinery to direct therapeutically relevant targets, including previously considered “undruggable” ones, for proteasomal degradation. PROTAC and other strategies targeting the ubiquitin proteasome system offer new therapeutic avenues which will expand the drug development toolboxes for glioblastoma. This review will provide a comprehensive overview of E3 ubiquitin ligases and deubiquitinating enzymes in the context of glioblastoma and their involvement in core signaling pathways including EGFR, TGF-β, p53 and stemness-related pathways. Finally, we offer new insights into how these ubiquitin-dependent mechanisms could be exploited therapeutically for glioblastoma.

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Section: Stem Cell Maintenancementioning

confidence: 98%

Targeting the Ubiquitin System in Glioblastoma

et al. 2020

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“…The mechanism remains unclear for the positive regulation of USP28 on c-MYC in human gliomas. 58 Bladder cancer It remains unclear for the role of USP28 in bladder cancer.…”

Section: Targeting Usp28 In Intestinal Cancermentioning

confidence: 99%

“…Importantly, USP28 promoted MYC expression, which was required for USP28-induced cell growth in human glioma. Therefore, USP28 could be a new target of therapy for human malignant gliomas 58 .…”

Section: Targeting Usp28 In Intestinal Cancermentioning

confidence: 99%

Targeting deubiquitinase USP28 for cancer therapy

et al. 2018

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As one of the most important post-translational modifications, ubiquitination plays versatile roles in cancer-related pathways, and is involved in protein metabolism, cell-cycle progression, apoptosis, and transcription. Counteracting the activities of the E3 ligases, the deubiquitylating enzymes have been suggested as another important mechanism to modulate the ubiquitination process, and are implicated in cancer as well. In this article, we review the emerging roles of USP28 in cancer pathways as revealed by recent studies. We discuss the major mechanisms by which USP28 is involved in the cancer-related pathways, whereby USP28 regulates physiological homeostasis of ubiquitination process, DNA-damage response, and cell cycle during genotoxic stress. We further review the studies where USP28 was targeted for treating multiples cancers including non-small cell lung cancer, breast cancer, intestinal cancers, gliomas, and bladder cancer. As a result, the clinical significance of targeting USP28 for cancer therapy merits further exploration and demonstration.

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“…In addition to its role in the p53 pathway, USP28 was also shown to stabilize the oncogene c-MYC after DNA damage. The same authors and others found high expression levels of this DUB in colon, lung, glioma, bladder, and breast carcinomas ( Popov et al, 2007a , b ; Diefenbacher et al, 2014 , 2015 ; Guo et al, 2014 ; Wang Z. et al, 2016 ). USP36 and USP37 also control the stability of c-Myc and thereby affect c-Myc oncogene driven cellular proliferation ( Zhang et al, 2006 ; Pan et al, 2015 ; Sun et al, 2015 ).…”

Section: Regulation Of P53 C-myc and Other Oncogenes By Dubsmentioning

confidence: 65%

DUBbing Cancer: Deubiquitylating Enzymes Involved in Epigenetics, DNA Damage and the Cell Cycle As Therapeutic Targets

Pinto-Fernández

Kessler

2016

Front. Genet.

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Controlling cell proliferation is one of the hallmarks of cancer. A number of critical checkpoints ascertain progression through the different stages of the cell cycle, which can be aborted when perturbed, for instance by errors in DNA replication and repair. These molecular checkpoints are regulated by a number of proteins that need to be present at the right time and quantity. The ubiquitin system has emerged as a central player controlling the fate and function of such molecules such as cyclins, oncogenes and components of the DNA repair machinery. In particular, proteases that cleave ubiquitin chains, referred to as deubiquitylating enzymes (DUBs), have attracted recent attention due to their accessibility to modulation by small molecules. In this review, we describe recent evidence of the critical role of DUBs in aspects of cell cycle checkpoint control, associated DNA repair mechanisms and regulation of transcription, representing pathways altered in cancer. Therefore, DUBs involved in these processes emerge as potentially critical targets for the treatment of not only hematological, but potentially also solid tumors.

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Ubiquitin-specific protease 28 is overexpressed in human glioblastomas and contributes to glioma tumorigenicity by regulating MYC expression

Cited by 22 publications

References 21 publications

Targeting the Ubiquitin System in Glioblastoma

Targeting the Ubiquitin System in Glioblastoma

Targeting deubiquitinase USP28 for cancer therapy

DUBbing Cancer: Deubiquitylating Enzymes Involved in Epigenetics, DNA Damage and the Cell Cycle As Therapeutic Targets

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