USP10 Antibody
Description
Introduction
The USP10 Antibody is a research tool designed to detect and analyze the ubiquitin-specific protease 10 (USP10) protein, a deubiquitinating enzyme critical for regulating protein stability and cellular processes. USP10 is implicated in immune regulation, cancer progression, and DNA repair mechanisms . This antibody is widely used in immunological and oncological studies to investigate USP10's role in diseases and therapeutic development.
Structure and Function of USP10
USP10 is a 798-amino acid protein containing a catalytic domain that removes ubiquitin from target proteins, stabilizing them and influencing pathways like DNA repair, cell cycle regulation, and apoptosis . In B cells, USP10 integrates B-cell receptor (BCR) and Toll-like receptor (TLR) signals to regulate activation-induced cytidine deaminase (AID), a key enzyme for antibody class-switching and somatic hypermutation . Its nuclear localization is controlled by phosphorylation, modulating immune responses to pathogens and vaccines .
Role in Immune Responses
USP10 is upregulated in germinal center B cells and activated B cells, where it stabilizes nuclear AID, enabling efficient antibody production against pathogens like SARS-CoV-2 and HIV-1 . Studies using USP10-deficient mice show impaired humoral immunity, reduced affinity maturation, and lower neutralizing antibody titers post-vaccination .
Cancer Implications
In non-small cell lung cancer (NSCLC), USP10 promotes cell invasion by stabilizing eukaryotic translation initiation factor 4 gamma 1 (EIF4G1), a protein involved in oncogenic signaling . USP10 overexpression correlates with tumor progression, while its knockdown suppresses metastatic potential .
Therapeutic Potential
Manipulating USP10 activity could enhance vaccine efficacy or inhibit cancer growth. For instance, targeting USP10 in B cells may improve nanoparticle-based vaccines, while its inhibition in tumors could reduce metastasis .
Applications of USP10 Antibody
The antibody is validated for:
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Western blot (WB): Detects endogenous USP10 in human, mouse, rat, and monkey samples .
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Immunoprecipitation (IP): Isolates USP10 for downstream analysis .
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Immunofluorescence (IF): Visualizes USP10 localization in cellular compartments .
| Antibody Source | Catalog # | Applications | Species Reactivity |
|---|---|---|---|
| Assay Genie | CAB7505 | WB, IF | Human, Mouse |
| Cell Signaling | #5553 | WB, IP, IF | Human, Mouse, Rat |
Product Specs
Target Background
- A genome-wide siRNA screen identified USP10 as a deubiquitinase for Slug in cancer cells. USP10 interacts with Slug and mediates its degradation by the proteasome. Notably, USP10 expression correlates with Slug expression in cancer biopsies. PMID: 29803676
- Loss of USP10 expression is linked to small intestinal adenocarcinoma. PMID: 30375264
- TP53 is one of USP10's targets. Wildtype TP53 is typically rescued from proteasomal degradation by USP10. Given that most KMT2A leukemias exhibit wildtype p53 alleles, disruption of an USP10 allele can be considered a pro-oncogenic event. PMID: 30107050
- Deubiquitylase USP10 interacts with RNF168 and TOP2alpha, inhibiting ubiquitylation of TOP2alpha and its chromatin binding. PMID: 27558965
- USP10 directly interacts with and stabilizes PTEN via deubiquitination. PMID: 28852924
- USP10 plays a regulatory role after wounding in determining myofibroblast development and activation of fibrotic TGFbeta signaling. PMID: 28851806
- Research has investigated USP10 expression in normal human adrenal glands and various adrenal tumors. USP10 protein was detected in 100% (30/30) adrenocortical adenomas, 88.89% (8/9) adrenocortical carcinomas, and 10% (2/20) pheochromocytomas. PMID: 26555087
- G3BP mediates stress granule condensation by shifting between two states controlled by phosphorylation of S149 and binding to Caprin1 or USP10. PMID: 27022092
- Data indicates that AMPK and USP10 form a positive feedforward loop, ensuring amplification of AMPK activation in response to fluctuations in cellular energy status. PMID: 26876938
- miR-191 promotes pancreatic cancer progression by targeting USP10, highlighting a novel mechanism for tumorigenesis. PMID: 25168367
- USP10 deubiquitinates and stabilizes SIRT6. PMID: 24332849
- Studies have identified USP10, a carboxyl-terminal ubiquitin-processing protease, as interacting with T-bet in the nucleus. PMID: 24845384
- USP10 acts as a host factor that inhibits stress-induced reactive oxygen species production and apoptosis in HTLV-1-infected T cells. PMID: 23775713
- Research has revealed a novel function for USP10 in facilitating the deubiquitination of CFTR in early endosomes, thereby enhancing CFTR's endocytic recycling and cell surface expression. PMID: 20215869
- Findings indicate that USP10 is a novel regulator of p53, offering an alternative mechanism for p53 inhibition in cancers with wild-type p53. PMID: 20096447
- Data suggests that USP10 is a new cofactor that binds to the androgen receptor (AR) and stimulates the androgen response of target promoters. This finding underscores the role of the ubiquitin/proteasome system in modulating AR function. PMID: 16368182
- RTQ-LDA and RTQ identified ubiquitin-specific protease 10 as significantly overexpressed in dead-of-disease compared to long-term survival glioblastoma multiforme patients. PMID: 16773218
- USP10 plays a role in facilitating the deubiquitination of CFTR in early endosomes, thereby enhancing the endocytic recycling of CFTR. PMID: 19398555
- Ras-GAP SH3 domain binding protein (G3BP) is a modulator of USP10. While G3BP doesn't appear to be a substrate of USP10, it inhibits USP10's ability to disassemble ubiquitin chains. PMID: 11439350
Q&A
What is the role of USP10 in cellular processes?
USP10, a ubiquitin-specific protease, plays a critical role in cellular mechanisms by regulating protein stability through deubiquitination. One of its key functions is stabilizing p53 by reversing Mdm2-induced nuclear export and degradation, particularly after DNA damage . USP10 also interacts with PTEN to prevent its K63-linked polyubiquitination mediated by TRIM25, thereby suppressing the AKT/mTOR signaling pathway . These activities underscore its importance in tumor suppression and cellular homeostasis.
How does USP10 influence antibody production?
USP10 directly regulates nuclear activation-induced cytidine deaminase (AID) activity, which is essential for class-switch recombination and somatic hypermutation in antibody genes. Signals from BCR (B-cell receptor) and TLR1/2 synergistically promote phosphorylation of USP10 at T674 within its nuclear localization signal (NLS) domain, enabling its nuclear translocation. This stabilization of AID protein enhances neutralizing antibody production following immunization with nanoparticle vaccines against pathogens like SARS-CoV-2 or HIV-1 .
What experimental systems are commonly used to study USP10?
USP10 antibody applications include Western blot (WB), immunoprecipitation (IP), immunofluorescence/immunocytochemistry (IF/ICC), immunohistochemistry (IHC), and enzyme-linked immunosorbent assay (ELISA). Positive detection has been reported in various cell lines such as HEK-293, MCF-7, Jurkat, and LNCaP cells . These systems allow researchers to investigate USP10's expression patterns, interactions with other proteins, and functional roles in different biological contexts.
How is USP10 involved in the DNA damage response?
USP10 stabilizes p53 by deubiquitinating it and facilitating its nuclear translocation during the DNA damage response. This process enhances p53's ability to activate downstream pathways that arrest the cell cycle or induce apoptosis . Additionally, USP10 does not affect PTEN transcription but reduces its polyubiquitination levels without altering protein stability , further contributing to genomic integrity.
What are the storage conditions for USP10 antibodies?
USP10 antibodies are typically stored at -20°C in PBS containing 0.02% sodium azide and 50% glycerol at pH 7.3. These conditions ensure stability for up to one year post-shipment without requiring aliquoting .
How can researchers optimize experimental protocols for detecting USP10?
Optimization depends on the specific application:
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For Western blotting (WB), dilutions range from 1:500 to 1:1000 for polyclonal antibodies or up to 1:50000 for monoclonal antibodies .
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Immunoprecipitation requires careful titration of antibody concentration, typically between 0.5–4 µg per 1–3 mg of total protein lysate .
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Immunofluorescence/immunocytochemistry protocols suggest dilutions between 1:50–1:500 for polyclonal antibodies or 1:200–1:800 for monoclonal antibodies .
It is recommended to test reagents in each experimental system to achieve optimal results.
How does USP10 interact with other proteins such as PTEN?
USP10 interacts with PTEN both ectopically and endogenously, as confirmed by immunoprecipitation/immunoblotting assays in HEK293T and NSCLC cell lines like A549 and H1299 . It colocalizes with PTEN predominantly in the cytoplasm and disrupts the interaction between PTEN and TRIM25, thereby preventing TRIM25-mediated K63-linked polyubiquitination of PTEN. These interactions highlight USP10's role in modulating signaling pathways critical for cancer progression.
What are the implications of USP10 deficiency in immune responses?
USP10 deficiency significantly reduces AID protein levels in B cells, impairing class-switch recombination and somatic hypermutation processes essential for antibody diversification . This leads to diminished neutralizing antibody production following vaccination against pathogens like SARS-CoV-2 or HIV-1. Such findings suggest that manipulating USP10 activity could enhance vaccine efficacy.
Can USP10 be targeted therapeutically to modulate immune or cancer-related pathways?
Yes, targeting USP10 offers therapeutic potential:
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In immune modulation, enhancing USP10 activity could improve antibody responses by stabilizing AID protein during vaccination .
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In oncology, inhibiting USP10 might suppress tumor growth by destabilizing p53 or altering PTEN ubiquitination dynamics .
Future studies should explore small molecules or genetic tools that selectively modulate USP10 function.
How does USP10 affect cellular proliferation and cycle progression?
USP10 prominently decreases cell viability in NSCLC models by arresting cells at the S phase of the cell cycle . This suppression of DNA synthesis aligns with PTEN's phosphatase activity, which inhibits AKT/mTOR signaling pathways involved in proliferation.
Data Tables Supporting Research Findings
| Application | Dilution Range | Cell Lines Tested | Observations |
|---|---|---|---|
| Western Blot | 1:500–1:50000 | HEK-293, MCF-7 | Positive detection |
| Immunoprecipitation | 0.5–4 µg per mg lysate | HEK-293 | Protein interaction studies |
| Immunofluorescence | 1:50–1:800 | HEK-293 | Colocalization studies |
| Immunohistochemistry | 1:500–2000 | Liver cancer tissues | Antigen retrieval required |
