USP22 Antagonizes p53 Transcriptional Activation by Deubiquitinating Sirt1 to Suppress Cell Apoptosis and Is Required for Mouse Embryonic Development

Lin, Zhenghong; Yang, Hee‐Young; Kong, Qingfei; Li, Jinping; Lee, Sang Myeong; Gao, Beixue; Dong, Hongxin; Wei, Jian‐Jun; Song, Jianxun; Zhang, Donna D.; Fang, Deyu

doi:10.1016/j.molcel.2012.03.024

Cited by 276 publications

(294 citation statements)

References 56 publications

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“…Loss of Gcn5 blocks oogenesis and metamorphosis (Carre et al 2005), and zygotic Ada2b is also essential for viability (Qi et al 2004;Pankotai et al 2005). Although their mutant phenotypes have not been compared, the mouse USP22-, GCN5-, or ADA3-null embryos all die during embryogenesis (Xu et al 2000;Lin et al 2012;Mohibi et al 2012). Additionally, GCN5 HAT activity is critical for cranial neural tube closure (Bu et al 2007).…”

Section: Discussionmentioning

confidence: 99%

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Enzymatic modules of the SAGA chromatin-modifying complex play distinct roles in Drosophila gene expression and development

Seidel

Szerszen

et al. 2017

Genes Dev.

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The Spt-Ada-Gcn5-acetyltransferase (SAGA) chromatin-modifying complex is a transcriptional coactivator that contains four different modules of subunits. The intact SAGA complex has been well characterized for its function in transcription regulation and development. However, little is known about the roles of individual modules within SAGA and whether they have any SAGA-independent functions. Here we demonstrate that the two enzymatic modules of Drosophila SAGA are differently required in oogenesis. Loss of the histone acetyltransferase (HAT) activity blocks oogenesis, while loss of the H2B deubiquitinase (DUB) activity does not. However, the DUB module regulates a subset of genes in early embryogenesis, and loss of the DUB subunits causes defects in embryogenesis. ChIP-seq (chromatin immunoprecipitation [ChIP] combined with high-throughput sequencing) analysis revealed that both the DUB and HAT modules bind most SAGA target genes even though many of these targets do not require the DUB module for expression. Furthermore, we found that the DUB module can bind to chromatin and regulate transcription independently of the HAT module. Our results suggest that the DUB module has functions within SAGA and independent functions.

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Section: Discussionmentioning

confidence: 99%

“…In Drosophila, the Non-stop (DUB) and Sgf11 function together in neural development . The mouse DUB USP22 is critical for the early embryogenesis (Lin et al 2012) and has also been shown to play a role in cell differentiation and lineage specification (Kosinsky et al 2015).…”

mentioning

confidence: 99%

Enzymatic modules of the SAGA chromatin-modifying complex play distinct roles in Drosophila gene expression and development

Seidel

Szerszen

et al. 2017

Genes Dev.

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“…Similarly, knockdown of USP7 resulted in a dramatic decrease in protein level of PHF8 in U2OS cells ( Figure 2B, left panel). However, knockdown of USP22, another nuclear deubiquitinase, had no evident effect on the expression level of PHF8 ( Figure 2C), while USP22 knockdown affected the protein abundance of SIRT1 (32). In addition, the decreased PHF8 protein expression under USP7 depletion was not a result of reduced PHF8 mRNA, as quantitative reverse transcription PCR (qRT-PCR) measurements indicated that USP7 knockdown did not result in alterations in PHF8 mRNA level in MCF-7 cells and ubiquitination (25).…”

Section: Introductionmentioning

confidence: 94%

Stabilization of histone demethylase PHF8 by USP7 promotes breast carcinogenesis

Wang¹,

Ma²,

Song³

et al. 2016

Journal of Clinical Investigation

167

172

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“…Cells (1x10 5 ) were seeded in 6-well plates overnight and subsequently SB203580 or dimethyl sulfoxide (DMSO) was added. After 12 h, the medium was changed for medium containing cisplatin for a further 12 or 24 h incubation.…”

Section: Total Rna Isolation and Quantitative Pcr (Qpcr)mentioning

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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USP22 Antagonizes p53 Transcriptional Activation by Deubiquitinating Sirt1 to Suppress Cell Apoptosis and Is Required for Mouse Embryonic Development

Cited by 276 publications

References 56 publications

Enzymatic modules of the SAGA chromatin-modifying complex play distinct roles in Drosophila gene expression and development

Enzymatic modules of the SAGA chromatin-modifying complex play distinct roles in Drosophila gene expression and development

Stabilization of histone demethylase PHF8 by USP7 promotes breast carcinogenesis

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

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