Structural Basis of the Interaction Between Ubiquitin Specific Protease 7 and Enhancer of Zeste Homolog 2

Gagarina, Varvara; Bojagora, Anna; Lacdao, Ira Kay; Luthra, Niharika; Pfoh, Roland; Mohseni, Sadaf; Chaharlangi, Danica; Tan, Nadine; Saridakis, V.

doi:10.1016/j.jmb.2019.12.026

Cited by 10 publications

(10 citation statements)

References 59 publications

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“…It was demonstrated in HCT116 cells that USP7 can interact with PRC1 and target the p16 locus to induce apoptosis [ 111 ]. USP7 can also control the EZH2 that is a functional enzymatic component of the PRC2 [ 112 ].…”

Section: Association Of Ubiquitin-specific Proteases (Usps) With Cancer-related Processesmentioning

confidence: 99%

Ubiquitin-Specific Proteases: Players in Cancer Cellular Processes

2021

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Ubiquitination represents a post-translational modification (PTM) essential for the maintenance of cellular homeostasis. Ubiquitination is involved in the regulation of protein function, localization and turnover through the attachment of a ubiquitin molecule(s) to a target protein. Ubiquitination can be reversed through the action of deubiquitinating enzymes (DUBs). The DUB enzymes have the ability to remove the mono- or poly-ubiquitination signals and are involved in the maturation, recycling, editing and rearrangement of ubiquitin(s). Ubiquitin-specific proteases (USPs) are the biggest family of DUBs, responsible for numerous cellular functions through interactions with different cellular targets. Over the past few years, several studies have focused on the role of USPs in carcinogenesis, which has led to an increasing development of therapies based on USP inhibitors. In this review, we intend to describe different cellular functions, such as the cell cycle, DNA damage repair, chromatin remodeling and several signaling pathways, in which USPs are involved in the development or progression of cancer. In addition, we describe existing therapies that target the inhibition of USPs.

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Section: Association Of Ubiquitin-specific Proteases (Usps) With Cancer-related Processesmentioning

confidence: 99%

Ubiquitin-Specific Proteases: Players in Cancer Cellular Processes

2021

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Section: Role Of Hausp In the Regulation Of Histone Post-translational Modificationsmentioning

confidence: 99%

“…Recently, EZH2 was identified as a novel HAUSP partner in human U2OS osteosarcoma cells and human HCT116 colorectal cancer cells [ 52 ]. The HAUSP–EZH2 interaction is mediated by the C-terminal region of HAUSP and the 489 PRKKKRK 495 region in EZH2 [ 52 ]. Both the depletion of HAUSP and its knockout in HCT116 cells reduced the expression levels of EZH2 protein and H3K27me3, whereas HAUSP reintroduction to HAUSP knockout HCT116 cells increased the protein expression levels of EZH2 [ 52 ].…”

Section: Role Of Hausp In the Regulation Of Histone Post-translational Modificationsmentioning

confidence: 99%

“…The HAUSP–EZH2 interaction is mediated by the C-terminal region of HAUSP and the 489 PRKKKRK 495 region in EZH2 [ 52 ]. Both the depletion of HAUSP and its knockout in HCT116 cells reduced the expression levels of EZH2 protein and H3K27me3, whereas HAUSP reintroduction to HAUSP knockout HCT116 cells increased the protein expression levels of EZH2 [ 52 ]. These findings indicate that HAUSP positively regulates the protein expression and activity of EZH2 and that the binding of EZH2 to HAUSP is essential both for the stability of EZH2 and for its function as an epigenetic writer of the trimethylation of H3 at K27 in cancer cells.…”

Section: Role Of Hausp In the Regulation Of Histone Post-translational Modificationsmentioning

confidence: 99%

“…Understanding the major factors regulating the expression and activity of chromatin effector proteins UHRF1 and DNMT1 could therefore unlock new secrets regarding the transmission of epigenetic patterns during cell division. HAUSP positions itself at the top of the regulatory hierarchies involved in the epigenetic silencing of TSGs in cancer due to its deubiquitinase activity and ability to team up through direct interactions with several epigenetic players ( Table 1 ) mainly the epigenetic reader UHRF1 [ 38 , 48 ]; DNMT1 [ 38 , 49 ]; the histone acetyltransferases TIP60 [ 50 ] and CBP (CREB binding protein) [ 51 ]; the histone lysine methyltransferases EZH2 (Enhancer of Zeste 2) [ 52 ] and MLL5 (Mixed-lineage leukemia 5) [ 53 ], and the lysine specific histone demethylases LSD1 (Lysine-specific demethylase 1) [ 54 , 55 ] and PHF8 (PHD finger protein 8) [ 56 ] ( Figure 2 ). The present review highlights the increasingly evident role of HAUSP as an epigenetic master regulator that governs a set of epigenetic players involved in the maintenance of DNA methylation and histone PTMs.…”

Section: Introductionmentioning

confidence: 99%

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HAUSP Is a Key Epigenetic Regulator of the Chromatin Effector Proteins

Abdullah

Alhosin

2021

Genes

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HAUSP (herpes virus-associated ubiquitin-specific protease), also known as Ubiquitin Specific Protease 7, plays critical roles in cellular processes, such as chromatin biology and epigenetics, through the regulation of different signaling pathways. HAUSP is a main partner of the “Epigenetic Code Replication Machinery,” ECREM, a large protein complex that includes several epigenetic players, such as the ubiquitin-like containing plant homeodomain (PHD) and an interesting new gene (RING), finger domains 1 (UHRF1), as well as DNA methyltransferase 1 (DNMT1), histone deacetylase 1 (HDAC1), histone methyltransferase G9a, and histone acetyltransferase TIP60. Due to its deubiquitinase activity and its ability to team up through direct interactions with several epigenetic regulators, mainly UHRF1, DNMT1, TIP60, the histone lysine methyltransferase EZH2, and the lysine-specific histone demethylase LSD1, HAUSP positions itself at the top of the regulatory hierarchies involved in epigenetic silencing of tumor suppressor genes in cancer. This review highlights the increasing role of HAUSP as an epigenetic master regulator that governs a set of epigenetic players involved in both the maintenance of DNA methylation and histone post-translational modifications.

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