The expression patterns of deubiquitinating enzymes, USP22 and Usp22

Lee, Hey-Jin; Kim, Myung-Sun; Shin, Jumi A.; Park, Tae‐Jin; Chung, Hyung-Min; Baek, Kwang‐Hyun

doi:10.1016/j.modgep.2005.07.007

Cited by 86 publications

(84 citation statements)

References 19 publications

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“…For example, USP22 mRNA is induced between days 4.5 and 6.5 of mouse embryogenesis (29). Furthermore, in genomewide assays in multiple cells lines, USP22 mRNA expression increases as ESCs differentiate in EBs (35).…”

Section: Usp22 Is Induced As Escsmentioning

confidence: 99%

“…First, Usp22 is part of an 11-gene cancer stem cell signature, where it regulates aggressive phenotypes, such as metastatic potential and resistance to therapy (26,28). Second, USP22 is required for embryonic development in mice (26,29). Third, the Drosophila USP22 ortholog Nonstop is required for proper neuronal development and the tissue-specific expression of SAGA-bound genes (30,31).…”

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confidence: 99%

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The Epigenetic Modifier Ubiquitin-specific Protease 22 (USP22) Regulates Embryonic Stem Cell Differentiation via Transcriptional Repression of Sex-determining Region Y-box 2 (SOX2)

Sussman

Stanek

Esteso

et al. 2013

Journal of Biological Chemistry

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Background: Ubiquitin-specific protease 22 (USP22) is a deubiquitylating enzyme with established biological functions in cancer cells. Results: USP22 drives differentiation of embryonic stem cells (ESCs) and represses sex-determining region Y-box 2 (SOX2) transcription. Conclusion: USP22 is induced during ESC differentiation to repress SOX2 transcription. Significance: Understanding the epigenetic programs that control changes in gene expression during the transition from self-renewal to differentiation.

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Section: Usp22 Is Induced As Escsmentioning

confidence: 99%

mentioning

confidence: 99%

The Epigenetic Modifier Ubiquitin-specific Protease 22 (USP22) Regulates Embryonic Stem Cell Differentiation via Transcriptional Repression of Sex-determining Region Y-box 2 (SOX2)

Sussman

Stanek

Esteso

et al. 2013

Journal of Biological Chemistry

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“…Ubiquitin-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).…”

Section: Introductionmentioning

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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“…As a component of the transcription regulatory histone acetylation complex SAGA, USP22 regulates gene transcription at an epigenetic level through the deubiquitination of histones, exerting broad biological functions, including cell cycle progression, embryonic development and telomere homeostasis (4)(5)(6). USP22 is expressed in numerous normal human tissues but is overexpressed in malignant tumors, such as colorectal, liver, breast, gastric, bladder and lung cancer, a showing correlation with tumor progression and metastasis (7)(8)(9)(10)(11)(12)(13)(14). Findings of these studies have demonstrated the importance of USP22 in cancer development; however, the role of USP22 in pancreatic cancer has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

Ubiquitin-specific protease 22-induced autophagy is correlated with poor prognosis of pancreatic cancer

et al. 2014

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Abstract. Ubiquitin-specific protease 22 (USP22) is a component of the transcription regulatory histone acetylation complex SAGA, which broadly regulates gene transcription and correlates with cancer progression, metastasis and prognosis. Autophagy is a cell pathway with dual functions that promotes cell survival or death. However, it is not known whether USP22 can regulate autophagy in pancreatic cancer. In the present study, we first identified that USP22 was overexpressed in a large number of pancreatic cancer patient samples, concomitant with the increased expression of LC3, a marker of autophagy. Statistical analysis revealed that the increase in USP22 and autophagy was positively correlated with poor prognosis of pancreatic cancer patients. Further investigation using a human pancreatic cancer cell (Panc-1) identified that the overexpression of USP22 increased the processing of LC3 into the active form LC3-II and the number of autophagosomes, thus leading to enhanced autophagy. Activation of ERK1/2 kinase rather than AKT1 by USP22 was found to be one of the mechanisms promoting LC3 processing. USP22-induced autophagy was also found to enhance cell proliferation and resistance to starvation and chemotherapeutic drugs in Panc-1 cells, therefore expressing an overall effect that promotes cell survival. Collectively, the present study demonstrated a new function of USP22 that induces autophagy, thus leading to the poor prognosis of pancreatic cancer.

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The expression patterns of deubiquitinating enzymes, USP22 and Usp22

Cited by 86 publications

References 19 publications

The Epigenetic Modifier Ubiquitin-specific Protease 22 (USP22) Regulates Embryonic Stem Cell Differentiation via Transcriptional Repression of Sex-determining Region Y-box 2 (SOX2)

The Epigenetic Modifier Ubiquitin-specific Protease 22 (USP22) Regulates Embryonic Stem Cell Differentiation via Transcriptional Repression of Sex-determining Region Y-box 2 (SOX2)

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

Ubiquitin-specific protease 22-induced autophagy is correlated with poor prognosis of pancreatic cancer

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