Cloning and Characterization of the Human USP22 Gene Promoter

Xiong, Jianjun; Che, Xiangxin; Yu, Huan; Gong, Zhizhong; Li, Weidong

doi:10.1371/journal.pone.0052716

Cited by 14 publications

(20 citation statements)

References 27 publications

(35 reference statements)

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“…These selectively inhibit ERK1/2, p38 MAPK and JNK, respectively. HeLa cells were transfected with the reporter construct, pGL-210/+52, which contains the USP22 basic promoter region from -210 to +52 (14). The transfected cells were cultured for a further 12 h in the presence of 2 µM U0126, 2 µM SB203580, 10 µM SP600125 and 0.1% DMSO as blank controls, and luciferase activity was measured.…”

Section: Resultsmentioning

confidence: 99%

p38 mitogen-activated protein kinase inhibits USP22 transcription in HeLa cells

et al. 2015

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Abstract. Elevated expression of ubiquitin-specific processing enzyme 22 (USP22) was identified in multiple types of human cancers, and was correlated with tumorigenesis and progression. Despite an increase in the numbers of studies in the physiological function of USP22, little is known regarding the regulation of its expression. The 5' flanking sequence of the USP22 gene was recently characterized. In the present study, USP22 transcription was regulated by p38 mitogen-activated protein kinase (MAPK). Treatment of human cervical carcinoma (HeLa) cells with SB203580, an inhibitor of p38 MAPK, enhanced basal USP22 promoter activity and mRNA abundance. Transfection of MAPK kinase 6 (MKK6), an upstream activator of p38 MAPK, resulted in a 40% decrease in USP22 mRNA, while the dominant negative MKK6 increased the transcription level of the USP22, similar to SB203580. Dual luciferase report assays showed that mutations of the Sp1 binding site ahead of the transcription start site abolished the promoting effect of the USP22 promoter by SB203580. Cisplatin, the activator of p38 MAPK, also suppressed USP22 expression. This suppression was blocked by SB203580. In conclusion, p38 MAPK acts as an upstream negative regulator of USP22 transcription in HeLa cells. IntroductionUbiquitin-specific processing enzyme 22 (USP22) is a novel deubiquitinating enzyme that can cleave ubiquitin (Ub) from Ub-conjugated protein substrates (1). As the subunit of the human SAGA coactivator complex, USP22 is linked to the regulation of gene transcription by deubiquitinating histones H2A and H2B (2,3). In addition, USP22 deubiquitinates intracellular protein, including the shelterin protein telomeric repeat binding factor 1 (4), the histone deacetylase sirtuin 1 (5) and the far upstream element-binding protein 1 fructose-1,6-bisphosphatase 1 (4), and therefore performs an extensive physiological function. A murine study showed that USP22 also regulates embryonic stem cell differentiation (6). In humans, the USP22 gene is located on chromosome 17, consists of 14 exons, and is transcribed and produced broadly across various tissues (7). Of note, elevated levels of USP22 have been identified in numerous types of human cancer, including colorectal (8) lung (9) and breast cancer (10). USP22 has been indicated in tumorigenesis. Deletion of USP22 leads to the accumulation of cells in the G 1 phase of the cell cycle (2). For these reasons, USP22 is a putative cancer stem cell marker. Reducing the rate of USP22 expression may be a suitable target for cancer therapy (11). However, the mechanisms that lead to USP22 transcriptional activation, particularly in the human tumor cells, remain unknown.Previously, USP22 transcription was activated by mitogen stimulation or viral infection in normal T and B lymphocytes (12), suggesting the regulation of USP22 gene expression occurs mainly at the transcriptional level. However, the mechanism in which signal transduction pathways regulate USP22 transcription is unclear. It is well-known that activation of the mito...

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Section: Resultsmentioning

confidence: 99%

p38 mitogen-activated protein kinase inhibits USP22 transcription in HeLa cells

et al. 2015

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“…At the transcriptional level, Sp1 and PKA/CREB have been reported to bind to USP22 promoter and regulate USP22 transcription [41, 42]. …”

Section: Usp22 Structure and Saga Deubiquitylase Module Formationmentioning

confidence: 99%

Ubiquitin-specific peptidase 22 functions and its involvement in disease

Melo‐Cardenas

Zhang

et al. 2016

Oncotarget

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Deubiquitylases remove ubiquitin moieties from different substrates to regulate protein activity and cell homeostasis. Since this posttranslational modification plays a role in several different cellular functions, its deregulation has been associated with different pathologies. Aberrant expression of the Ubiquitin-Specific Peptidase 22 (USP22) has been associated with poor cancer prognosis and neurological disorders. However, little is known about USP22 role in these pathologies or in normal physiology. This review summarizes the current knowledge about USP22 function from yeast to human and provides an overview of the possible mechanisms by which USP22 is emerging as a potential oncogene.

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“…Although USP22 is considered a promising biomarker for NB diagnosis and prognosis, [5][6][7][8][9][18][19][20] little is known about its effect in NB. Indeed, it is involved in the effective prediction of the response to therapy in individual patients with cancer.…”

Section: Discussionmentioning

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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Cloning and Characterization of the Human USP22 Gene Promoter

Cited by 14 publications

References 27 publications

p38 mitogen-activated protein kinase inhibits USP22 transcription in HeLa cells

p38 mitogen-activated protein kinase inhibits USP22 transcription in HeLa cells

Ubiquitin-specific peptidase 22 functions and its involvement in disease

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

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