Steady-state kinetic studies reveal that the anti-cancer target Ubiquitin-Specific Protease 17 (USP17) is a highly efficient deubiquitinating enzyme

Hjortland, Nicole M.; Mesecar, Andrew D.

doi:10.1016/j.abb.2016.10.008

Cited by 7 publications

(2 citation statements)

References 28 publications

(72 reference statements)

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“…This effect may have been accentuated by the up-regulation of other implied genes such as Rhoj, which can evoke focal adhesion disassembly (Wilson et al, 2014), and Eps8l1, which can activate Rac, leading to the reorganization of the actin cytoskeleton (Offenhauser et al, 2004). Moreover, cell cycle arrest may have been repressed due to the up-regulation of Usp2 and Usp17le, since they promote the stabilization of cyclin D1 (Shan et al, 2009) and Cdc25A (Hjortland & Mesecar, 2016), respectively. Supporting these results, Ptprd and Ptprr tumor suppressor genes were down-regulated in the technological group.…”

Section: Discussionmentioning

confidence: 99%

The role of osmolarity adjusting agents in the regulation of encapsulated cell behavior to provide a safer and more predictable delivery of therapeutics

et al. 2017

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Transplantation of cells within alginate microspheres has been extensively studied for sustained drug delivery. However, the lack of control over cell behavior represents a major concern regarding the efficacy and the safety of the therapy. Here, we demonstrated that when formulating the biosystem, an adequate selection of osmolarity adjusting agents significantly contributes to the regulation of cell responses. Our data showed that these agents interact in the capsule formation process, influencing the alginate crosslinking degree. Therefore, when selecting inert or electrolyte-based osmolarity adjusting agents to encapsulate D1 multipotent mesenchymal stromal cells (MSCs), alginate microcapsules with differing mechanical properties were obtained. Since mechanical forces acting on cells influence their behavior, contrasting cell responses were observed both, in vitro and in vivo. When employing mannitol as an inert osmolarity adjusting agent, microcapsules presented a more permissive matrix, allowing a tumoral-like behavior. This resulted in the formation of enormous cell-aggregates that presented necrotic cores and protruding peripheral cells, rendering the therapy unpredictable, dysfunctional, and unsafe. Conversely, the use of electrolyte osmolarity adjusting agents, including calcium or sodium, provided the capsule with a suitable crosslinking degree that established a tight control over cell proliferation and enabled an adequate therapeutic regimen in vivo. The crucial impact of these agents was confirmed when gene expression studies reported pivotal divergences not only in proliferative pathways, but also in genes involved in survival, migration, and differentiation. Altogether, our results prove osmolarity adjusting agents as an effective tool to regulate cell behavior and obtain safer and more predictable therapies.ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 99%

The role of osmolarity adjusting agents in the regulation of encapsulated cell behavior to provide a safer and more predictable delivery of therapeutics

et al. 2017

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“…The USP domain is located near the N-terminus, and HABMs are located at amino acids 401–409 and 445–453 near the C-terminus. Each USP domain contains a catalytic component [Cys, Asp (I), His, and Asp/Asn (II)] and is responsible for deubiquitination activity [ 32 ]. HABMs exist in the C-terminus of USP17 subfamily members, except in USP17N.…”

Section: Structure Of Dub3/usp17mentioning

confidence: 99%

The role of the deubiquitinating enzyme DUB3/USP17 in cancer: a narrative review

Yang

Zhang

et al. 2021

Cancer Cell Int

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The balance between ubiquitination and deubiquitination is critical for the degradation, transport, localization, and activity of proteins. Deubiquitinating enzymes (DUBs) greatly contribute to the balance of ubiquitination and deubiquitination, and they have been widely studied due to their fundamental role in cancer. DUB3/ubiquitin-specific protease 17 (USP17) is a type of DUB that has attracted much attention in cancer research. In this review, we summarize the biological functions and regulatory mechanisms of USP17 in central nervous system, head and neck, thoracic, breast, gastrointestinal, genitourinary, and gynecologic cancers as well as bone and soft tissue sarcomas, and we provide new insights into how USP17 can be used in the management of cancer.

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USP17-mediated de-ubiquitination and cancer: Clients cluster around the cell cycle

Ducker

Shaw

2021

The International Journal of Biochemistry & Cell Biology

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Steady-state kinetic studies reveal that the anti-cancer target Ubiquitin-Specific Protease 17 (USP17) is a highly efficient deubiquitinating enzyme

Abstract: Graphical abstract

Cited by 7 publications

References 28 publications

The role of osmolarity adjusting agents in the regulation of encapsulated cell behavior to provide a safer and more predictable delivery of therapeutics

The role of osmolarity adjusting agents in the regulation of encapsulated cell behavior to provide a safer and more predictable delivery of therapeutics

The role of the deubiquitinating enzyme DUB3/USP17 in cancer: a narrative review

USP17-mediated de-ubiquitination and cancer: Clients cluster around the cell cycle

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