Suppression of USP7 negatively regulates the stability of ETS proto-oncogene 2 protein

Park, Hong-Beom; Min, Yosuk; Hwang, Sohyun; Baek, Kwang‐Hyun

doi:10.1016/j.biopha.2023.114700

Cited by 3 publications

(6 citation statements)

References 69 publications

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“…However, in our initial screening, USP7 was not identified as one of the sixteen ETS2-binding DUBs and, therefore, was excluded from our study, and we did not characterize its function on ETS2. Additionally, the endogenous expression levels of ETS2 were decent and appeared to be relatively unstable within a 12-24 h timeframe in the cell lines tested by the authors [18]. In contrast, in our study, endogenous ETS2 was rarely detectable, possibly due to differences in cellular context, necessitating the examination of overexpressed MYC-ETS2 instead.…”

Section: Discussioncontrasting

confidence: 67%

“…In a recent study, Park et al demonstrated that the suppression of USP7 led to the inhibition of ETS2 deubiquitination and promoted its protein degradation [18]. However, in our initial screening, USP7 was not identified as one of the sixteen ETS2-binding DUBs and, therefore, was excluded from our study, and we did not characterize its function on ETS2.…”

Section: Discussionmentioning

confidence: 89%

“…This result clearly suggests that USP39 antagonizes the transcriptional activity of ETS2, which may be partly due to the reduced nuclear localization caused by the deubiquitination of ETS2. Recently, Park et al demonstrated that USP7 deubiquitinates and activates the transcriptional activity of ETS2 [18]. We wondered whether USP7 and USP39 have different effects on ETS2 s transcriptional activity.…”

Section: Usp39 Represses the Transcriptional Activity Of Ets2 Partly ...mentioning

confidence: 97%

“…ETS1 was identified as a target of USP9X with NRAS regulatory potential in a USP9X ubiquitylome analysis [17]. Furthermore, USP7 has more recently been recognized as a DUB for ETS2, which was predicted as a substrate protein through the analysis of publicly available proteomic databases [18]. In both studies, the DUBs regulated protein stability by inhibiting the proteasomal degradation of ETS1 and ETS2.…”

Section: Introductionmentioning

confidence: 99%

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USP39-Mediated Non-Proteolytic Control of ETS2 Suppresses Nuclear Localization and Activity

Choi,

Lee,

Kim

et al. 2023

Biomolecules

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ETS2 is a member of the ETS family of transcription factors and has been implicated in the regulation of cell proliferation, differentiation, apoptosis, and tumorigenesis. The aberrant activation of ETS2 is associated with various human cancers, highlighting its importance as a therapeutic target. Understanding the regulatory mechanisms and interacting partners of ETS2 is crucial for elucidating its precise role in cellular processes and developing novel strategies to modulate its activity. In this study, we conducted binding assays using a human deubiquitinase (DUB) library and identified USP39 as a novel ETS2-binding DUB. USP39 interacts with ETS2 through their respective amino-terminal regions, and the zinc finger and PNT domains are not required for this binding. USP39 deubiquitinates ETS2 without affecting its protein stability. Interestingly, however, USP39 significantly suppresses the transcriptional activity of ETS2. Furthermore, we demonstrated that USP39 leads to a reduction in the nuclear localization of ETS2. Our findings provide valuable insights into the intricate regulatory mechanisms governing ETS2 function. Understanding the interplay between USP39 and ETS2 may have implications for therapeutic interventions targeting ETS2-related diseases, including cancer, where the dysregulation of ETS2 is frequently observed.

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Section: Discussioncontrasting

confidence: 67%

Section: Discussionmentioning

confidence: 89%

Section: Usp39 Represses the Transcriptional Activity Of Ets2 Partly ...mentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

USP39-Mediated Non-Proteolytic Control of ETS2 Suppresses Nuclear Localization and Activity

Choi,

Lee,

Kim

et al. 2023

Biomolecules

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show abstract

“…For example, certain DUBs, including BAP1, UCHL1, CYLD, and USP22, exhibit intrinsic oncogenic or tumor-suppressor activities [ 51 ]. Moreover, DUBs like USP22 play a role in promoting tumor development through the regulation of epigenetic changes [ 53 , 54 ], while others such as USP28 and USP7 are involved in controlling the turnover of oncogenes or tumor suppressors [ 55 , 56 ].…”

Section: Targeting Enzymes Of the Ubiquitin–proteasome Systemmentioning

confidence: 99%

Ubiquitin Engineering for Interrogating the Ubiquitin–Proteasome System and Novel Therapeutic Strategies

Tang,

Marchand,

Veggiani

2023

Cells

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Protein turnover, a highly regulated process governed by the ubiquitin–proteasome system (UPS), is essential for maintaining cellular homeostasis. Dysregulation of the UPS has been implicated in various diseases, including viral infections and cancer, making the proteins in the UPS attractive targets for therapeutic intervention. However, the functional and structural redundancies of UPS enzymes present challenges in identifying precise drug targets and achieving target selectivity. Consequently, only 26S proteasome inhibitors have successfully advanced to clinical use thus far. To overcome these obstacles, engineered peptides and proteins, particularly engineered ubiquitin, have emerged as promising alternatives. In this review, we examine the impact of engineered ubiquitin on UPS and non-UPS proteins, as well as on viral enzymes. Furthermore, we explore their potential to guide the development of small molecules targeting novel surfaces, thereby expanding the range of druggable targets.

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Current and future directions of USP7 interactome in cancer study

Park,

Baek

2023

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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Suppression of USP7 negatively regulates the stability of ETS proto-oncogene 2 protein

Cited by 3 publications

References 69 publications

USP39-Mediated Non-Proteolytic Control of ETS2 Suppresses Nuclear Localization and Activity

USP39-Mediated Non-Proteolytic Control of ETS2 Suppresses Nuclear Localization and Activity

Ubiquitin Engineering for Interrogating the Ubiquitin–Proteasome System and Novel Therapeutic Strategies

Current and future directions of USP7 interactome in cancer study

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