Ubiquitin-Specific Peptidase 7: A Novel Deubiquitinase That Regulates Protein Homeostasis and Cancers

Zhou, Lin; Ouyang, Taohui; Li, Meihua; Hong, Tao; Mhs, Alriashy; Wang, Meng; Zhang, Na

doi:10.3389/fonc.2021.784672

Cited by 9 publications

(5 citation statements)

References 119 publications

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“…Modulation of ubiquitination was also evident as a strategy of betaretroviral PRs. Putative docking with cell signaling associated ubiquitin-specific protease 7 [USP7/ HAUSP (49,50)] was also a conserved prediction for all betaretroviral PRs. Specifically, ERVK PR contains a conserved USP7 TRAF domain (MATH) P/A-xx-S binding motif (ADVS, aa.…”

Section: Characterization Of Eukaryotic Linear Motifs In Ervk Proteas...mentioning

confidence: 99%

“…ERVK PR was unique in its propensity to putatively interact with proliferating cell nuclear antigen (PCNA) (55), as it contained two overlapping PCNA-interacting protein (PIP) motifs (aa. [41][42][43][44][45][46][47][48][49][50][51][52][53][54][55], also known as a PIP box, just prior to the PR flap domain (Figure 1, Table 1). In addition, only ERVK PR contained an Nterminal SxIP motif (Figure 1, aa.…”

Section: Characterization Of Eukaryotic Linear Motifs In Ervk Proteas...mentioning

confidence: 99%

“…USP7 is a deubiquitinating enzyme that plays a significant role in cell signaling through its regulation of substrate stability and degradation (86). Predicted to interact with all betaretroviral PRs, USP7 is a ubiquitin-specific protease which plays a role in DDR, immune response, epigenetic control, and cancer (49,50). USP7 is targeted in viral evasion of innate immunity, with Pathways associated with ERVK protease interactome.…”

Section: Ervk Protease Is Associated With the Apex Of Ubiquitin-like ...mentioning

confidence: 99%

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Predicted cellular interactors of the endogenous retrovirus-K protease enzyme

Narvey¹,

Vandenakker²,

Rempel³

et al. 2022

Front. Virol.

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Retroviral proteases are essential enzymes for viral replication and drive changes within the cellular proteome. While several studies have demonstrated that protease (PR) enzymes from exogenous retroviruses cleave cellular proteins and modulate cellular signaling, the impact of PRs encoded by endogenous retroviruses within the human genome has been largely overlooked. One human symbiont called Endogenous retrovirus-K (ERVK) is pathologically associated with both neurological disease and cancers. Using a computational biology approach, we sought to characterize the ERVK PR interactome. The ERVK PR protein sequence was analyzed using the Eukaryotic Linear Motif (ELM) database and results compared to ELMs of other betaretroviral PRs and similar endogenated viral PRs. A list of putative ERVK PR cellular protein interactors was curated from the ELM list and submitted for STRING analysis to generate an ERVK PR interactome. Reactome analysis was used to identify key pathways potentially influenced by ERVK PR. Network analysis postulated that ERVK PR interacts at the apex of several ubiquitination pathways, as well as has a role in the DNA damage response, gene regulation, and intracellular trafficking. Among retroviral PRs, a predicted interaction with proliferating cell nuclear antigen (PCNA) was unique to ERVK PR. The most prominent disease-associated pathways identified were viral carcinogenesis and neurodegeneration. This strengthens the role of ERVK PR in these pathologies by putatively driving alterations in cellular signaling cascades via select protein-protein interactions.

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Section: Characterization Of Eukaryotic Linear Motifs In Ervk Proteas...mentioning

confidence: 99%

Section: Characterization Of Eukaryotic Linear Motifs In Ervk Proteas...mentioning

confidence: 99%

Section: Ervk Protease Is Associated With the Apex Of Ubiquitin-like ...mentioning

confidence: 99%

See 1 more Smart Citation

Predicted cellular interactors of the endogenous retrovirus-K protease enzyme

Narvey¹,

Vandenakker²,

Rempel³

et al. 2022

Front. Virol.

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“…Ubiquitination is a crucial posttranslational modification (PTM) that supports intracellular signal transduction and controls the localization, stability, and activity of numerous proteins [ 1 , 2 , 3 ]. A certain class of proteases known as deubiquitinases (DUBs), or deubiquitinating enzymes can reverse the ubiquitination process.…”

Section: Introductionmentioning

confidence: 99%

USP7 Inhibitors in Cancer Immunotherapy: Current Status and Perspective

Korenev

Yakukhnov

Druk

et al. 2022

Cancers

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Ubiquitin-specific protease 7 (USP7) regulates the stability of a plethora of intracellular proteins involved in the suppression of anti-tumor immune responses and its overexpression is associated with poor survival in many cancers. USP7 impairs the balance of the p53/MDM2 axis resulting in the proteasomal degradation of the p53 tumor suppressor, a process that can be reversed by small-molecule inhibitors of USP7. USP7 was shown to regulate the anti-tumor immune responses in several cases. Its inhibition impedes the function of regulatory T cells, promotes polarization of tumor-associated macrophages, and reduces programmed death-ligand 1 (PD‑L1) expression in tumor cells. The efficacy of small-molecule USP7 inhibitors was demonstrated in vivo. The synergistic effect of combining USP7 inhibition with cancer immunotherapy is a promising therapeutic approach, though its clinical efficacy is yet to be proven. In this review, we focus on the recent developments in understanding the intrinsic role of USP7, its interplay with other molecular pathways, and the therapeutic potential of targeting USP7 functions.

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“…10,11 USP7 is a DUB known to be associated with a variety of tumour-suppressor genes and proto-oncogenes, pointing to its significance in tumour biology and progression. 12,13 USP7 exhibits high expression levels in numerous cancer tissues and often correlates with poor prognosis and metastasis. It is a key regulator of the tumour suppressor p53 either via direct interaction, 14 or indirectly by stabilizing mouse double minute 2 homolog (MDM2), that is the E3 ligase, which facilitates ubiquitination and degradation of p53.…”

mentioning

confidence: 99%