Ubiquitin-specific peptidase 22 functions and its involvement in disease

Melo‐Cardenas, Johanna; Zhang, Yusi; Zhang, Donna D.; Fang, Deyu

doi:10.18632/oncotarget.8602

Cited by 75 publications

(73 citation statements)

References 72 publications

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“…Whereas oncogenic c‐Myc is the cause of transformation and tumorigenesis in many malignancies, USP22 is also upregulated in certain types of cancer, suggesting that USP22 might possess oncogenic properties (Melo‐Cardenas, Zhang, Zhang, & Fang, ). To investigate whether altered expression of USP22 is closely linked with c‐Myc in human cancers, we searched public databases such as the cancer microarray database Oncomine.…”

Section: Resultsmentioning

confidence: 99%

Deubiquitinating enzyme USP22 positively regulates c‐Myc stability and tumorigenic activity in mammalian and breast cancer cells

Kim

Hong

Park

et al. 2017

Journal Cellular Physiology

115

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The proto-oncogene c-Myc has a pivotal function in growth control, differentiation, and apoptosis and is frequently affected in human cancer, including breast cancer. Ubiquitin-specific protease 22 (USP22), a member of the USP family of deubiquitinating enzymes (DUBs), mediates deubiquitination of target proteins, including histone H2B and H2A, telomeric repeat binding factor 1, and cyclin B1. USP22 is also a component of the mammalian SAGA transcriptional co-activating complex. In this study, we explored the functional role of USP22 in modulating c-Myc stability and its physiological relevance in breast cancer progression. We found that USP22 promotes deubiquitination of c-Myc in several breast cancer cell lines, resulting in increased levels of c-Myc. Consistent with this, USP22 knockdown reduces c-Myc levels. Furthermore, overexpression of USP22 stimulates breast cancer cell growth and colony formation, and increases c-Myc tumorigenic activity. In conclusion, the present study reveals that USP22 in breast cancer cell lines increases c-Myc stability through c-Myc deubiquitination, which is closely correlated with breast cancer progression.

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Section: Resultsmentioning

confidence: 99%

Deubiquitinating enzyme USP22 positively regulates c‐Myc stability and tumorigenic activity in mammalian and breast cancer cells

Kim

Hong

Park

et al. 2017

Journal Cellular Physiology

115

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“…USP22 is a key subunit of the Spt‐Ada‐Gcn5 acetyl transferase complex (SAGA), which removes ubiquitin from target proteins to regulate the transcription of downstream genes (Reyes‐Turcu et al ., ). USP22 plays a significant role both in pathology and in physiology via interactions with different substrates (Melo‐Cardenas et al ., ). USP22 could bind to TRF1 and regulate telomere length (Atanassov et al ., ).…”

Section: Introductionmentioning

confidence: 97%

“…USP22 could bind to TRF1 and regulate telomere length (Atanassov et al ., ). USP22 deubiquitinates cyclin B1, stabilizes cyclin B1 by antagonizing proteasome‐mediated degradation, and promotes it accumulation in the nucleus (Lin et al ., ; Melo‐Cardenas et al ., ). Recently, USP22 was found to cooperate with GSK3β to stabilize KDM1A and further promote glioblastoma tumorigenesis (Zhou et al ., ).…”

Section: Introductionmentioning

confidence: 97%

USP22 mediates the multidrug resistance of hepatocellular carcinoma via the SIRT1/AKT/MRP1 signaling pathway

Ling

Shan

et al. 2017

Mol Oncol

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Drug treatments for hepatocellular carcinoma (HCC) often fail because of multidrug resistance (MDR). The mechanisms of MDR are complex but cancer stem cells (CSCs), which are able to self‐renew and differentiate, have recently been shown to be involved. The deubiquitinating enzyme ubiquitin‐specific protease 22 (USP22) is a marker for CSCs. This study aimed to elucidate the role of USP22 in MDR of HCC and the underlying mechanisms. Using in vitro and in vivo assays, we found that modified USP22 levels were responsible for the altered drug‐resistant phenotype of BEL7402 and BEL/FU cells. Downregulation of USP22 dramatically inhibited the expression of ABCC1 (encoding MRP1) but weakly influenced ABCB1 (encoding P‐glycoprotein). Sirtuin 1 (SIRT1) was reported previously as a functional mediator of USP22 that could promote HCC cell proliferation and enhance resistance to chemotherapy. In this study, USP22 directly interacted with SIRT1 and positively regulated SIRT1 protein expression. Regulation of the expression of both USP22 and SIRT1 markedly affected the AKT pathway and MRP1 expression. Inhibition of the AKT pathway by its specific inhibitor LY294002 resulted in downregulation of MRP1. USP22 and MRP1 expression was detected in 168 clinical HCC samples by immunohistochemical staining, and a firm relationship between USP22 and MRP1 was identified. Together, these results indicate that USP22 could promote the MDR in HCC cells by activating the SIRT1/AKT/MRP1 pathway. USP22 might be a potential target, through which the MDR of HCC in clinical setting could be reversed.

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“…[5][6][7][8][9] USP22, as a component of the human Spt-Ada-Gcn5-acetyltransferase (hSAGA) complex, is at the core of several physiological and pathological processes and is directly implicated in cell-cycle progression and transcriptional regulation. 10 As a multi-subunit complex, hSAGA is organized into several functional submodules, including the deubiquitinating module (DUB), the histone acetyltransferase (HAT) module, and the suppressor of Ty (SPT) and TATA-binding protein-associated factor (TAF) modules. The USP22 is the essential protein linked to the DUB module.…”

Section: Introductionmentioning

confidence: 99%

Ubiquitin-specific protease 22 is associated with poor prognosis in neuroblastoma

Qu¹,

Liu²

2020

Adv Clin Exp Med

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Background. Ubiquitin-specific protease 22 (USP22) alters histone ubiquitination and is considered to be an oncogenic factor involved in tumor progression. The USP22 aberrance has been implicated in several malignancies, but whether USP22 plays a role in neuroblastoma (NB) remains unclear. To the best of our knowledge, the clinicopathological significance of USP22 expression in NB has not been previously reported in the English-language medical literature.Objectives. The aim of this study was to investigate the role of USP22 and its association with potential targets in patients with NB.Material and methods. The potential clinicopathological significance of USP22 expression in NB was studied using immunohistochemistry, immunohistochemical staining assessment and statistical analyses.Results. Based on the immunohistochemical analysis, the USP22 protein was detected more manifestly in NB tissues than in healthy peritumoral tissue. Furthermore, an association between USP22, lymph node metastasis and NB clinical stage was observed, whereby the level of USP22 protein was higher in stage III-IV specimens than in stage I-II specimens (p < 0.05). Furthermore, tumors expressing USP22 were associated with poorer patient prognosis than the USP22-negative tumors. The multivariate Cox regression analysis suggested that the level of USP22 protein is a predictive factor for survival (p < 0.05). Conclusions.Our results indicate a significant association between USP22 level and poor prognosis in NB. Thus, USP22 represents a valuable biomarker for predicting the outcome of patients with NB.

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Ubiquitin-specific peptidase 22 functions and its involvement in disease

Cited by 75 publications

References 72 publications

Deubiquitinating enzyme USP22 positively regulates c‐Myc stability and tumorigenic activity in mammalian and breast cancer cells

Deubiquitinating enzyme USP22 positively regulates c‐Myc stability and tumorigenic activity in mammalian and breast cancer cells

USP22 mediates the multidrug resistance of hepatocellular carcinoma via the SIRT1/AKT/MRP1 signaling pathway

Ubiquitin-specific protease 22 is associated with poor prognosis in neuroblastoma

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