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- Table of Contents
Facts about Ubiquitin carboxyl-terminal hydrolase 7.
Hydrolase Which deubiquitinates target proteins such as FOXO4, p53/TP53, MDM2, ERCC6, DNMT1, UHRF1, PTEN, KMT2E/MLL5 and DAXX (PubMed:11923872, PubMed:15053880, PubMed:16964248, PubMed:18716620, PubMed:25283148, PubMed:26678539).
Together with DAXX, prevents MDM2 self-ubiquitination and enhances the E3 ligase activity of MDM2 towards p53/TP53, thereby promoting p53/TP53 ubiquitination and proteasomal degradation (PubMed:15053880, PubMed:16845383, PubMed:18566590, PubMed:20153724).Deubiquitinates p53/TP53, preventing degradation of p53/TP53, and enhances p53/TP53-dependent transcription regulation, cell growth repression and apoptosis (PubMed:25283148). Deubiquitinates p53/TP53 and MDM2 and strongly stabilizes p53/TP53 even in the presence of extra MDM2, and also induces p53/TP53-dependent cell growth repression and apoptosis (PubMed:11923872).
Human | |
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Gene Name: | USP7 |
Uniprot: | Q93009 |
Entrez: | 7874 |
Belongs to: |
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peptidase C19 family |
Deubiquitinating enzyme 7; EC 3.1.2.15; EC 3.4.19.12; HAUSP; HAUSPTEF1; Herpes virus-associated ubiquitin-specific protease; Herpesvirus-associated ubiquitin-specific protease; TEF1; ubiquitin carboxyl-terminal hydrolase 7; ubiquitin specific peptidase 7 (herpes virus-associated); ubiquitin specific protease 7 (herpes virus-associated); Ubiquitin thioesterase 7; Ubiquitin-specific-processing protease 7; USP7
Mass (kDA):
128.302 kDA
Human | |
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Location: | 16p13.2 |
Sequence: | 16; NC_000016.10 (8892094..8963912, complement) |
Widely expressed. Overexpressed in prostate cancer.
Nucleus. Cytoplasm. Nucleus, PML body. Chromosome. Present in a minority of ND10 nuclear bodies. Association with ICP0/VMW110 at early times of infection leads to an increased proportion of USP7-containing ND10. Colocalizes with ATXN1 in the nucleus. Colocalized with DAXX in speckled structures. Colocalized with PML and PTEN in promyelocytic leukemia protein (PML) nuclear bodies.
In biological tests the use of antibodies to USP7 are used to detect the protein. They are either monoclonal, or multiclonal and react with USP7 from various animal samples. Boster Bio has developed antibodies against USP7 that react with different biological samples. Their antibody portfolio includes antibodies against rabbit and mouse. The ICP0/VMW110 protein increases the amount of USP7 in ND10 and PML body proteins colocalize with USP7 in the nucleus. It is also known that PTEN (a protein from promyelocytic Leukemia) is colocalized inside the human lymphocytes of the nucleus with USP7.
USP7 is an important member of the DUB family, and it has been shown to be associated with negative immune regulation. The expression of USP7 is negatively related to PD-L1, TGF-b, and TGF-b, and positively with SATB1. The use of USP7 could increase the level of anti-tumor immunity. There are many questions regarding the role of USP7 in tumors.
Cancer patients may be activated by USP7, that can trigger anti-tumor immunity. It targets USP7 decreases CD4+ T cells, while increasing the number of CD8+ T cell and CTLs. USP7 also enhances CD8+ T cell counts and does not affect Treg cells. The anti-tumor effects of USP7 on cancer cells are promising and warrant further investigation.
A recent study revealed that conditional deletion of UsP7 in Foxp3-positive Treg cells leads to rapidly lethal autoimmunity. Additionally, Usp7-/ mice also develop autoantibodies to pancreatic islet cells and gastric parietal cells. Therefore, USP7mice carry an increased risk of developing tumors.
USP7 plays a major role in preventing M2 function in murine M2 cell lines. Using RTPCR, the presence common genes that are associated with DUBs were observed in M2 cells and MPhs induced with the ANA-1. In addition, USP7 was expressed in BMDMs in a similar way to CD206.
Interestingly, USP7 inhibition also activates the JNK/ERK/p38 MAPK pathway MPhs and TAMs. However, the mechanism behind this is not well understood. It is also not clear whether USP7 inhibition can boost anti-tumor immunity in human patients. This research is currently in progress. However, it is important to note that USP7-targeted T cells could prove beneficial in the treatment of cancer.
The ubiquitin-proteasome (UPA) pathway is a key mechanism for protein degradation. Ubiquitin-modifying enzymes (DUBs) eliminate the ubiquitin chains that are in proteins. They regulate various cell functions. The treatment for cancer has shown promise using inhibitors of DUB proteins. While more research is required to better understand the role played by USP7 in anti-tumor immunity the potential for cancer immunotherapy is substantial.
The targeting of USP7 expression in cancer cells could be a significant factor in the treatment of this disease. USP7 promotes epithelial-mesenchymal transition, a hallmark of tumor growth. It also interacts with the ATM-dependent phosphatase PPM1G. This study suggests that USP7 expression could be associated with poor prognosis for certain kinds of cancer.
The expression of USP7 in the prostate is linked to the aggressiveness of the cancer. Multiple myeloma cells that become resistant to conventional chemotherapy and bortezomib could survive if USP7 inhibition was used. In addition the high USP7 levels could trigger the growth of tumors. Further research is required to determine the way in which the USP7 gene interacts with and influences tumor growth.
A large number of tumor cells express the USP7 protein. Patients with a defective ATM/p53 have higher levels of USP7 expression. However, it is unclear whether this effect occurs through the immune system of tumors or another mechanism. In this study, USP7 inhibitor P5091 was proven to significantly slow down the growth of the CT26 tumor cell line and its weight. P5091 also inhibits Treg cell growth by suppressing FOXP3 transcription.
USP7 is a herpesvirus-associated ubiquitin-specific protease (HASP) that deubiquitinates p53 and several key regulatory proteins including PTEN, INK4a, and TSPYL5. It also inhibits expression of several transcription factors, including CDC-promox as well as TP53. Targeting USP7 is crucial for cancer research.
USP7 inhibition inhibits HCC cell growth and can be used to boost chemotherapy. USP7 inhibitors have shown not to enhance the growth of HCC cells due to their ability to increase HRR-inducing chemotherapy. This suggests that USP7 inhibition could improve the efficacy of current cancer therapies. Although there isn't enough evidence to support this idea however, it is clear that USP7 inhibitors might play an effect on the treatment of HCC.
The results of this study show that inhibition of USP7 reduces the tumor-growth-promoting protein DDR. The translocation of the apoptosis-inducing proteins (tAIF) is also affected by inhibition of USP7. USP7 inhibition is believed to be a possible target for HCC drugs. This study was funded by grants from the Natural Science Foundation of China and the Teaching Research Project of Affiliated Hospital of Nantong University.
Efficacy of targeting USP7 is an option for treating lung cancer. This target is expressed in LUADs. Its inhibition slows down the progression of tumors and increases the immune response. Targeting USP7 in combination with immunotherapy may have beneficial effects on lung cancer. This study investigated the expression of USP7 in 51 DUB genes. Furthermore, USP7 inhibitors induced functional and phenotypic changes to M2 MPhs.
USP7 has been shown to be associated in some human GC tissues with the expression of PD-1. USP7 was shown to reduce the expression of PDL1 in human GC cells. However, the USP7 knockout cells showed decreased expression of PD-1. Furthermore, USP7-sgRNA-lentivirus inhibited PD-L1 degradation in MFC cells.
Targeting USP7 triggers anti-tumor immune responses in TME. Targeting USP7 increases TAM polarization into M1 MPhs. Additionally targeting USP7 can inhibit tumor growth and triggers anti-tumor immune responses in TME. It also blocks the growth of tumor cells by reducing the number of T cells that are CD4+ and increasing the number of CD8+ T cells. Although USP7 targeting isn't an effective treatment for cancer, it can offer hope to patients who are suffering from cancer.
Combining immunotherapy and USP7 targeting has been proven to increase the overall survival rate of patients with multiple forms of cancer. It has been shown that overexpression of USP7 in cancer cells correlates with malignant phenotype and poor prognosis. It also regulates the P53-MDM2-P53 Axis, a key player in tumor development. It is essential to know the precise role played by USP7 in the progression of tumors.
The inhibition of USP7 in cancer cells has produced promising results. USP7 inhibition inhibits tumor growth and reduces the expression of mPD-L1. The targeting of USP7 in mice blocks MGC-803 function. The USP7 inhibition affects Treg function, it also enhances the ability of tumor cells to kill cells. While USP7 is harmful and inhibits tumor growth there are some adverse reactions.
In MGC-803 cells, USP7 expression was reduced after it was genetically eliminated. USP7 inhibition inhibited the expression of the PD-L1 gene within MFC SGC-7901 cells and BGC-823 cells. USP7 inhibition has also shown promising results when combined with immunotherapy. While further research is needed to confirm the effectiveness of these treatments and effectiveness, the potential for USP7 inhibition could be increased.
The WD40 repeat is a structural motif that contains tryptophan and the aspartic acid that acts as a substrate for a variety of USP protein. USP7 is well-integrated with many of these proteins. However, one specific interaction was identified through mass spectrometry analyses on a large scale. BUB3, a mitotic checkpoint protein that plays a key role in correct microtubule-kinetochore attachment, is another USP7 substrate. Its deubiquitination regulates ARF4 expression, and targeting BUB3 can inhibit ARF4 activity and boost its expression.
Recent research has shown that cells lacking levels of USP7 expression exhibit an incredibly higher mitotic defect rate (compared to cells that are in control). Additionally cells with decreased USP7 expression show more apoptosis, and increased activity of caspase 3. These findings suggest that USP7 is a significant element in mitotic progression and targeting this enzyme may be a good strategy. However it is important to note that targeting USP7 on its own can cause a myriad of problems.
Researchers studied the expression of USP7 genes in tumors as well as normal tissues to address these problems. In prostate cancer and lung cancer, the depletion of USP7 induces apoptosis via mitotic catastrophe. A USP7 inhibitor can also trigger an apoptosis in cancer cells that are not susceptible to mitotic catastrophe. Combining with other agents that inhibit mitotic kinase PLK1, USP7 can be used to treat lung cancer. It is also targeted at MDR1 or ABCB.
In addition, it regulates the ubiquitin-proteasome system, USP7 protects substrate proteins tagged with ubiquitin. USP7 is responsible for ensuring the stability of the oncogenic protein p53, by inhibiting nuclear translocation. Additionally the targeting of USP7 alone may prove to be a crucial cancer treatment. If successful, USP7 inhibition will lead to cell death, which is crucial in preventing metastasis.
These effects aren't the only ones. USP7 inhibitors also have an important apoptotic effect on GBM cells. Additionally, the drug P5091 blocks the ARF4-mediated ubiquitination. In the study, P5091 decreased GBM cell growth, and enhanced expression of apoptosis-related proteins. The drug also decreased expression of ARF4 and BCL2-related proteins.
PMID: 9034339 by Everett R.D., et al. A novel ubiquitin-specific protease is dynamically associated with the PML nuclear domain and binds to a herpesvirus regulatory protein.
PMID: 12093161 by Hong S., et al. USP7, a ubiquitin-specific protease, interacts with ataxin-1, the SCA1 gene product.