Dataset Information

Monitoring Target Engagement of Deubiquitylating Enzymes Using Activity Probes: Past, Present, and Future.

ABSTRACT: Deubiquitylating enzymes or DUBs are a class of enzymes that selectively remove the polypeptide posttranslational modification ubiquitin from a number of substrates. Approximately 100 DUBs exist in human cells and are involved in key regulatory cellular processes, which drive many disease states, making them attractive therapeutic targets. Several aspects of DUB biology have been studied through genetic knock-out or knock-down, genomic, or proteomic studies. However, investigation of enzyme activation and regulation requires additional tools to monitor cellular and physiological dynamics. A comparison between genetic ablation and dominant-negative target validation with pharmacological inhibition often leads to striking discrepancies. Activity probes have been used to profile classes of enzymes, including DUBs, and allow functional and dynamic properties to be assigned to individual proteins. The ability to directly monitor DUB activity within a native biological system is essential for understanding the physiological and pathological role of individual DUBs. We will discuss the evolution of DUB activity probes, from in vitro assay development to their use in monitoring DUB activity in cells and in animal tissues, as well as recent progress and prospects for assessing DUB inhibition in vivo.

SUBMITTER: Harrigan J

PROVIDER: S-EPMC7120244 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Monitoring Target Engagement of Deubiquitylating Enzymes Using Activity Probes: Past, Present, and Future.

Harrigan Jeanine J Jacq Xavier X

Methods in molecular biology (Clifton, N.J.) 20160101

Deubiquitylating enzymes or DUBs are a class of enzymes that selectively remove the polypeptide posttranslational modification ubiquitin from a number of substrates. Approximately 100 DUBs exist in human cells and are involved in key regulatory cellular processes, which drive many disease states, making them attractive therapeutic targets. Several aspects of DUB biology have been studied through genetic knock-out or knock-down, genomic, or proteomic studies. However, investigation of enzyme acti ...[more]

PMID: 27613052

Similar Datasets

Project description:Steady progress in contraception research has been achieved over the past 50 years. Hormonal and nonhormonal modern contraceptives have improved women's lives by reducing different health conditions that contributed to considerable morbidity. However, the contraceptives available today are not suitable to all users, and the need to expand contraceptive choices still exists. Novel products such as new implants, contraceptive vaginal rings, transdermal patches and newer combinations of oral contraceptives have recently been introduced in family planning programs, and hormonal contraception is widely used for spacing and limiting births. Concerns over the adverse effects of hormonal contraceptives have led to research and development of new combinations with improved metabolic profile. Recent developments include use of natural compounds such as estradiol and estradiol valerate with the hope to decrease thrombotic risk, in combination with newer progestins derived from the progesterone structure or from spirolactone, in order to avoid the androgenic effects. Progesterone antagonists and progesterone receptor modulators are highly effective in blocking ovulation and preventing follicular rupture and are undergoing investigations in the form of oral pills and in semi-long-acting delivery systems. Future developments also include the combination of a contraceptive with an antiretroviral agent for dual contraception and protection against sexually transmitted diseases, to be used before intercourse or on demand, as well as for continuous use in dual-protection rings. Although clinical trials of male contraception have reflected promising results, limited involvement of industry in that area of research has decreased the likelihood of having a male method available in the current decade. Development of nonhormonal methods is still at an early stage of research, with the identification of specific targets within the reproductive system in ovaries and testes, as well as interactions between spermatozoa and ova. It is hoped that the introduction of new methods with additional health benefits would help women and couples with unmet needs to obtain access to a wider range of contraceptives with improved acceptability.

Dataset Information

Monitoring Target Engagement of Deubiquitylating Enzymes Using Activity Probes: Past, Present, and Future.

Publications

Monitoring Target Engagement of Deubiquitylating Enzymes Using Activity Probes: Past, Present, and Future.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets