Редактирование: USP7

Ubiquitin carboxyl-terminal hydrolase 7 (EC 3.4.19.12) (Deubiquitinating enzyme 7) (Herpesvirus-associated ubiquitin-specific protease) (Ubiquitin thioesterase 7) (Ubiquitin-specific-processing protease 7) [HAUSP]

==Publications==

{{medline-entry
|title=Deubiquitinase [[USP7]] regulates [i]Drosophila[/i] aging through ubiquitination and autophagy.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33221768
|abstract=Ubiquitination-mediated protein degradation is the selective degradation of diverse forms of damaged proteins that are tagged with ubiquitin, while deubiquitinating enzymes reverse ubiquitination-mediated protein degradation by removing the ubiquitin chain from the target protein. The interactions of ubiquitinating and deubiquitinating enzymes are required to maintain protein homeostasis. The ubiquitin-specific protease [[USP7]] is a deubiquitinating enzyme that indirectly plays a role in repairing DNA damage and development. However, the mechanism of its participation in aging has not been fully explored. Regarding this issue, we found that [[USP7]] was necessary to maintain the normal lifespan of [i]Drosophila melanogaster[/i], and knockdown of [i]dusp7[/i] shortened the lifespan and reduced the ability of [i]Drosophila[/i] to cope with starvation, oxidative stress and heat stress. Furthermore, we showed that the ability of [[USP7]] to regulate aging depends on the autophagy and ubiquitin signaling pathways. Furthermore, 2,5-dimethyl-celecoxib (DMC), a derivative of celecoxib, can partially restore the shortened lifespan and aberrant phenotypes caused by [i]dusp7[/i] knockdown. Our results suggest that [[USP7]] is an important factor involved in the regulation of aging, and related components in this regulatory pathway may become new targets for anti-aging treatments.

|keywords=* DMC
* Drosophila
* USP7
* aging
* autophagy
|full-text-url=https://sci-hub.do/10.18632/aging.104067
}}
{{medline-entry
|title=Inhibition of [[USP7]] activity selectively eliminates senescent cells in part via restoration of p53 activity.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32064756
|abstract=The accumulation of senescent cells (SnCs) is a causal factor of various age-related diseases as well as some of the side effects of chemotherapy. Pharmacological elimination of SnCs (senolysis) has the potential to be developed into novel therapeutic strategies to treat these diseases and pathological conditions. Here we show that ubiquitin-specific peptidase 7 ([[USP7]]) is a novel target for senolysis because inhibition of [[USP7]] with an inhibitor or genetic depletion of [[USP7]] by RNA interference induces apoptosis selectively in SnCs. The senolytic activity of [[USP7]] inhibitors is likely attributable in part to the promotion of the human homolog of mouse double minute 2 (MDM2) ubiquitination and degradation by the ubiquitin-proteasome system. This degradation increases the levels of p53, which in turn induces the pro-apoptotic proteins PUMA, NOXA, and [[FAS]] and inhibits the interaction of BCL-XL and BAK to selectively induce apoptosis in SnCs. Further, we show that treatment with a [[USP7]] inhibitor can effectively eliminate SnCs and suppress the senescence-associated secretory phenotype (SASP) induced by doxorubicin in mice. These findings suggest that small molecule [[USP7]] inhibitors are novel senolytics that can be exploited to reduce chemotherapy-induced toxicities and treat age-related diseases.

|keywords=* MDM2
* Senescence
* USP7
* apoptosis
* p53
* senolytics
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059172
}}
{{medline-entry
|title=Disruption of the Phosphate Transporter Pit1 in Hepatocytes Improves Glucose Metabolism and Insulin Signaling by Modulating the [[USP7]]/[[IRS1]] Interaction.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27568561
|abstract=The liver plays a central role in whole-body lipid and glucose homeostasis. Increasing dietary fat intake results in increased hepatic fat deposition, which is associated with a risk for development of insulin resistance and type 2 diabetes. In this study, we demonstrate a role for the phosphate inorganic transporter 1 (PiT1/SLC20A1) in regulating metabolism. Specific knockout of Pit1 in hepatocytes significantly improved glucose tolerance and insulin sensitivity, enhanced insulin signaling, and decreased hepatic lipogenesis. We identified [[USP7]] as a PiT1 binding partner and demonstrated that Pit1 deletion inhibited [[USP7]]/[[IRS1]] dissociation upon insulin stimulation. This prevented [[IRS1]] ubiquitination and its subsequent proteasomal degradation. As a consequence, delayed insulin negative feedback loop and sustained insulin signaling were observed. Moreover, PiT1-deficient mice were protected against high-fat-diet-induced obesity and diabetes. Our findings indicate that PiT1 has potential as a therapeutic target in the context of metabolic syndrome, obesity, and diabetes.
|mesh-terms=* Adipose Tissue
* Aging
* Animals
* Diet, High-Fat
* Fatty Liver
* Fibroblasts
* Gluconeogenesis
* Glucose
* Glucose Tolerance Test
* Hepatocytes
* Inflammation
* Insulin
* Insulin Receptor Substrate Proteins
* Insulin Resistance
* Mice, Knockout
* Obesity
* Organ Specificity
* Phenotype
* Phosphorylation
* Protein Binding
* Proto-Oncogene Proteins c-akt
* Receptor, Insulin
* Signal Transduction
* Transcription Factor Pit-1
* Ubiquitin-Specific Peptidase 7
* Ubiquitination
* Weight Gain

|full-text-url=https://sci-hub.do/10.1016/j.celrep.2016.08.012
}}
{{medline-entry
|title=The C. elegans Ortholog of [[USP7]] controls DAF-16 stability in Insulin/IGF-1-like signaling.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27123371
|abstract=FOXO family transcription factors are downstream effectors of Insulin/IGF-1 signaling (IIS) and are regulated by posttranslational modification and coregulators, including components of the ubiquitin-proteasome system (UPS). Cofactors promoting DAF-16/FOXO protein stability and function in IIS have not been described yet. In a recent study, we have identified the deubiquitylating enzyme MATH-33, the ortholog of mammalian [[USP7]]/HAUSP, as an essential DAF-16 coregulator. We found that MATH-33 actively stabilizes DAF-16 protein levels when IIS is downregulated. Here we discuss how DAF-16/FOXO transcription factors are regulated by the UPS, in particular by the interplay of E3-ubiquitin ligases and deubiquitylating enzymes, which is critical for balancing DAF-16/FOXO activity and degradation. Recent findings raise the intriguing possibility that regulated oscillations in DAF-16/FOXO steady state levels play an integral role in mechanisms controlling healthspan and lifespan extension. 

|keywords=* DAF-16
* DUB
* FOXO
* HAUSP
* Insulin/IGF-1 signaling
* MATH-33
* RLE-1
* USP7
* aging
* deubiquitinating enzyme
* longevity
* ubiquitin proteasome system
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826154
}}