USP22, an hSAGA subunit and potential cancer stem cell marker, reverses the polycomb-catalyzed ubiquitylation of histone H2A

Zhang, Xiaoyong; Pfeiffer, Harla K.; Thorne, Alan W.; McMahon, Steven B.

doi:10.4161/cc.7.11.5962

Cited by 138 publications

(139 citation statements)

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“…In yeast lacking Sgf73, Sus1 is released from SAGA but is still recruited to genes, albeit at a reduced level (Pascual-Garcia et al 2008). Moreover, early reports identified USP22 as an H2Aub deubiquitinase acting on polycomb-regulated genes (Zhang et al 2008). In principal, SAGA may release subcomplexes to participate in diverse functions.…”

Section: Loss Of Ataxin-7 Reduces H2b Ubiquitination Genes and Developmmentioning

confidence: 99%

Loss of Drosophila Ataxin-7, a SAGA subunit, reduces H2B ubiquitination and leads to neural and retinal degeneration

et al. 2014

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The Spt-Ada-Gcn5-acetyltransferase (SAGA) chromatin-modifying complex possesses acetyltransferase and deubiquitinase activities. Within this modular complex, Ataxin-7 anchors the deubiquitinase activity to the larger complex. Here we identified and characterized Drosophila Ataxin-7 and found that reduction of Ataxin-7 protein results in loss of components from the SAGA complex. In contrast to yeast, where loss of Ataxin-7 inactivates the deubiquitinase and results in increased H2B ubiquitination, loss of Ataxin-7 results in decreased H2B ubiquitination and H3K9 acetylation without affecting other histone marks. Interestingly, the effect on ubiquitination was conserved in human cells, suggesting a novel mechanism regulating histone deubiquitination in higher organisms. Consistent with this mechanism in vivo, we found that a recombinant deubiquitinase module is active in the absence of Ataxin-7 in vitro. When we examined the consequences of reduced Ataxin-7 in vivo, we found that flies exhibited pronounced neural and retinal degeneration, impaired movement, and early lethality.

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Section: Loss Of Ataxin-7 Reduces H2b Ubiquitination Genes and Developmmentioning

confidence: 99%

Loss of Drosophila Ataxin-7, a SAGA subunit, reduces H2B ubiquitination and leads to neural and retinal degeneration

et al. 2014

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“…Many of these enzymes, including MYSM1 (Zhu et al, 2007), USP16 (also known as Ubp-M) (Joo et al, 2007), USP21 (Nakagawa et al, 2008) and Drosophila Calypso (BAP1 in mammals) (Scheuermann et al, 2010) act on monoubiquitylated H2A (H2AUb), whereas the Lys63-specific DUB BRCC3 shows specificity for diubiquitylated H2A (Feng et al, 2010) and USP10 specifically acts on the H2AZ variant (Draker et al, 2011). Other DUBs that can deubiquitylate both H2A and H2B include USP3 (Nicassio et al, 2007), Xenopus laevis USP12 and USP46 (Joo et al, 2011), and USP22 (Ubp8 in yeast) (Zhang et al, 2008a;Zhang et al, 2008b). In yeast and flies, H2B is the histone that is predominantly ubiquitylated, and this is processed by Ubp10 and Ubp8 in yeast, and USP7 in flies and mammalian cells (Frappier and Verrijzer, 2011;Gardner et al, 2005;Sarkari et al, 2010;van der Knaap et al, 2005).…”

Section: Dubs As Histone Modifiersmentioning

confidence: 99%

Cellular functions of the DUBs

Clague

Coulson

Urbé

2012

Journal of Cell Science

194

166

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SummaryUbiquitylation is a reversible post-translational modification that has emerged as a key regulator of most complex cellular processes. It may rival phosphorylation in scope and exceed it in complexity. The dynamic nature of ubiquitylation events is important for governing protein stability, maintaining ubiquitin homeostasis and controlling ubiquitin-dependent signalling pathways. The human genome encodes ~80 active deubiquitylating enzymes (DUBs, also referred to as deubiquitinases), which exhibit distinct specificity profiles towards the various ubiquitin chain topologies. As a result of their ability to reverse ubiquitylation, these enzymes control a broad range of key cellular processes. In this Commentary we discuss the cellular functions of DUBs, such as their role in governing membrane traffic and protein quality control. We highlight two key signalling pathways -the Wnt and transforming growth factor  (TGF-) pathways, for which dynamic ubiquitylation has emerged as a key regulator. We also discuss the roles of DUBs in the nucleus, where they govern transcriptional activity and DNA repair pathways.

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“…ubH2A and ubH2B signals were detected using the LI-COR Odyssey Infrared Imaging System (Lincoln, NE) and IR dye-conjugated secondary antibodies (1:5,000) as described by the manufacturer. FLAG-USP22 plasmid was kindly provided by Dr. Steven McMahon, and FLAG-USP22 was purified as described previously (29,50).…”

Section: Usp12 and Usp46 Knockdown Reverse Transcription-polymerase mentioning

confidence: 99%

Regulation of Histone H2A and H2B Deubiquitination and Xenopus Development by USP12 and USP46

Joo¹,

Jones²,

Yang³

et al. 2011

Journal of Biological Chemistry

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Post-translational histone modifications play important roles in regulating gene expression programs, which in turn determine cell fate and lineage commitment during development. One such modification is histone ubiquitination, which primarily targets histone H2A and H2B. Although ubiquitination of H2A and H2B has been generally linked to gene silencing and gene activation, respectively, the functions of histone ubiquitination during eukaryote development are not well understood. Here, we identified USP12 and USP46 as histone H2A and H2B deubiquitinases that regulate Xenopus development. USP12 and USP46 prefer nucleosomal substrates and deubiquitinate both histone H2A and H2B in vitro and in vivo. WDR48, a WD40 repeat-containing protein, interacts with USP12 and USP46 and is required for the histone deubiquitination activity. Overexpression of either gene leads to gastrulation defects without affecting mesodermal cell fate, whereas knockdown of USP12 in Xenopus embryos results in reduction of a subset of mesodermal genes at gastrula stages. Immunohistochemical staining and chromatin immunoprecipitation assays revealed that USP12 regulates histone deubiquitination in the mesoderm and at specific gene promoters during Xenopus development. Taken together, this study identifies USP12 and USP46 as histone deubiquitinases for H2A and H2B and reveals that USP12 regulates Xenopus development during gastrula stages.Eukaryotic development requires precise control of gene expression patterns that are essential for cellular identity and differentiation (1, 2). Genomic DNA in eukaryotic cells is organized into a chromatin structure by association with histone and non-histone proteins (3, 4), and the structure of chromatin is believed to play a critical role in regulating chromatin-templated nuclear processes such as transcription (5, 6). Post-translational modifications of histones represent a major mechanism by which cells control the structure and function of chromatin. An increasing list of histone-modifying enzymes and histone modifications has been shown to be critical for normal development and to play causal roles in the pathogenesis of certain human diseases (7-9).Of the vast variety of histone modifications, histone ubiquitination is unique, in which a 76-amino acid bulky protein is attached primarily to histone H2A and H2B (10, 11). The recent characterization of ubiquitin ligase hPRC1L and deubiquitinase Ubp-M (USP16) for histone H2A revealed critical functions for this modification in gene silencing, X inactivation, cell cycle progression, and DNA damage repair (12-15). In addition to Ubp-M, 2A-DUB (MYSM1) and USP21 were also identified as H2A-specific deubiquitinases (16,17). These enzymes might function in different cellular processes, for example, 2A-DUB in androgen receptor-mediated gene activation and USP21 in liver regeneration (16,17). Recently, the Drosophila PcG gene calypso was found to encode a ubiquitin C-terminal hydrolase BAP1, which specifically deubiquitinates histone H2A and regulates Hox gene r...

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USP22, an hSAGA subunit and potential cancer stem cell marker, reverses the polycomb-catalyzed ubiquitylation of histone H2A

Cited by 138 publications

References 16 publications

Loss of Drosophila Ataxin-7, a SAGA subunit, reduces H2B ubiquitination and leads to neural and retinal degeneration

Loss of Drosophila Ataxin-7, a SAGA subunit, reduces H2B ubiquitination and leads to neural and retinal degeneration

Cellular functions of the DUBs

Regulation of Histone H2A and H2B Deubiquitination and Xenopus Development by USP12 and USP46

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