Regulation of USP28 Deubiquitinating Activity by SUMO Conjugation

Zhen, Yang; Knobel, Philip A.; Stracker, Travis H.; Reverter, David

doi:10.1074/jbc.m114.601849

Cited by 29 publications

(31 citation statements)

References 49 publications

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“…(141). Similar mechanisms may be in place for USP28 (140). Another DUB that is subjected to inhibitory SUMOylation is CYLD, in which SUMOylation in the N terminus inactivates the C-terminal catalytic domain (142).…”

Section: Depending On Whether Lys99 Is Modified With Ubiquitin or Summentioning

confidence: 86%

“…The c-Myc-stabilizing oncogenic DUB USP28 (135) and its relative USP25, which is upregulated after viral infection (136) and regulates toll-like receptor and interleukin signaling (137,138), are pharmacologically interesting enzymes regulated by SUMO modifications (139,140). In USP25, three N-terminal UBDs modulate DUB activity, and monoubiquitination of Lys99 located at the beginning of a UIM activates the enzyme (141).…”

Section: Sumoylationmentioning

confidence: 99%

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Mechanisms of Deubiquitinase Specificity and Regulation

Mevissen

Komander²

2017

Annu. Rev. Biochem.

726

646

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Protein ubiquitination is one of the most powerful posttranslational modifications of proteins, as it regulates a plethora of cellular processes in distinct manners. Simple monoubiquitination events coexist with more complex forms of polyubiquitination, the latter featuring many different chain architectures. Ubiquitin can be subjected to further posttranslational modifications (e.g., phosphorylation and acetylation) and can also be part of mixed polymers with ubiquitin-like modifiers such as SUMO (small ubiquitin-related modifier) or NEDD8 (neural precursor cell expressed, developmentally downregulated 8). Together, cellular ubiquitination events form a sophisticated and versatile ubiquitin code. Deubiquitinases (DUBs) reverse ubiquitin signals with equally high sophistication. In this review, we conceptualize the many layers of specificity that DUBs encompass to control the ubiquitin code and discuss examples in which DUB specificity has been understood at the molecular level. We further discuss the many mechanisms of DUB regulation with a focus on those that modulate catalytic activity. Our review provides a framework to tackle lingering questions in DUB biology.

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Section: Depending On Whether Lys99 Is Modified With Ubiquitin or Summentioning

confidence: 86%

Section: Sumoylationmentioning

confidence: 99%

Mechanisms of Deubiquitinase Specificity and Regulation

Mevissen

Komander²

2017

Annu. Rev. Biochem.

726

646

View full text Add to dashboard Cite

show abstract

“…Binding of OTUB1 and E2 enzymes, including UbcH5 and Ubc13, also regulates OTUB1 enzymatic activity towards K48 ubiquitin chains [ 81 ]. Usp28 on the other hand can be regulated by SUMOylation at the N -terminal domain, this has a negative effect on its deubiquitinase activity [ 82 ].…”

Section: Regulation Of Epigenetics By Deubiquitinationmentioning

confidence: 99%

Deubiquitinating enzymes as oncotargets

McClurg

Robson

2015

Oncotarget

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Carcinogenesis is a complex process tightly regulated at multiple levels by post-translational modifications. Epigenetics plays a major role in cancer development, all stable changes to the gene expression process that are not a result of a direct change in the DNA code are described as epigenetics. Epigenetic processes are regulated by post-translational modifications including ubiquitination which can directly affect either histones or transcription factors or may target their co-factors and interacting partners exerting an indirect effect. Deubiquitination of these target proteins is equally important and alterations in this pathway can also lead to cancer development, progression and metastasis. Only the correct, unaltered balance between ubiquitination and deubiquitination ensures healthy cellular homeostasis. In this review we focus on the role of deubiquitinating (DUB) enzymes in various aspects of epigenetics including the regulation of transcription factors, histone modifications, DNA damage repair pathways and cell cycle regulation. We discuss the impact of those processes on tumourigenesis and potential therapeutic applications of DUBs for cancer treatment.

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“…Ubiquitination was first reported as a mechanism to mark proteins for proteasome-mediated degradation. Later, more functions of ubiquitination have been revealed, spanning from modulating protein trafficking to regulating activities of enzymes 1 .…”

Section: Introductionmentioning

confidence: 99%

Targeting deubiquitinase USP28 for cancer therapy

et al. 2018

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As one of the most important post-translational modifications, ubiquitination plays versatile roles in cancer-related pathways, and is involved in protein metabolism, cell-cycle progression, apoptosis, and transcription. Counteracting the activities of the E3 ligases, the deubiquitylating enzymes have been suggested as another important mechanism to modulate the ubiquitination process, and are implicated in cancer as well. In this article, we review the emerging roles of USP28 in cancer pathways as revealed by recent studies. We discuss the major mechanisms by which USP28 is involved in the cancer-related pathways, whereby USP28 regulates physiological homeostasis of ubiquitination process, DNA-damage response, and cell cycle during genotoxic stress. We further review the studies where USP28 was targeted for treating multiples cancers including non-small cell lung cancer, breast cancer, intestinal cancers, gliomas, and bladder cancer. As a result, the clinical significance of targeting USP28 for cancer therapy merits further exploration and demonstration.

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Regulation of USP28 Deubiquitinating Activity by SUMO Conjugation

Cited by 29 publications

References 49 publications

Mechanisms of Deubiquitinase Specificity and Regulation

Mechanisms of Deubiquitinase Specificity and Regulation

Deubiquitinating enzymes as oncotargets

Targeting deubiquitinase USP28 for cancer therapy

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