PCNA Monoclonal Antibody
Description
Introduction to PCNA Monoclonal Antibodies
Proliferating Cell Nuclear Antigen (PCNA) is a 36 kDa homotrimeric protein critical for DNA replication, repair, and chromatin remodeling. PCNA monoclonal antibodies are engineered to bind specific epitopes of this protein, enabling its detection and functional analysis in research and clinical diagnostics. These antibodies are widely used to assess cell proliferation rates, study DNA repair mechanisms, and identify cancer biomarkers .
Structure and Function of PCNA
PCNA acts as a sliding clamp for DNA polymerases during replication and repair, forming a ring-shaped structure around DNA to enhance processivity. Key interactions include:
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DNA replication: Scaffolds polymerases (δ, ε, η) and ligases .
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DNA repair: Coordinates repair pathways (base excision, nucleotide excision, mismatch repair) .
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Cell cycle regulation: Overexpression correlates with S-phase progression and cancer virulence .
Applications in Research and Diagnostics
PCNA monoclonal antibodies are employed across diverse methodologies:
Epitope Mapping and Specificity
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PC10 (Clone PC10): Binds linear epitopes in the aa 111–125 region, showing nuclear localization and simpler epitope recognition compared to other antibodies (e.g., 19A2, 19F4) .
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1C11: Targets aa 151–261, with reactivity in human, mouse, rat, and rabbit .
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mAb14: Unique antibody detecting cell surface PCNA in lymphoma cells, distinct from nuclear-targeting antibodies .
Prognostic Value in Cancer
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Ampulla of Vater cancer: PCNA-positive rates >40% correlate with poor prognosis and metastasis .
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Cutaneous T-cell lymphoma: mAb14 identifies malignant cells in Sézary syndrome via cell surface PCNA detection .
Therapeutic Potential
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PCNA-targeting peptides: Induce apoptosis in neuroblastoma, prostate, breast, and bladder cancers .
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mAb14: Blocks NKp44-PCNA interaction, enhancing NK cell activity against lymphoma .
Comparative Analysis of PCNA Antibodies
Challenges and Limitations
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Epitope masking: Formalin fixation may obscure nuclear PCNA epitopes, requiring antigen retrieval .
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Cross-reactivity variability: PC10 detects non-human primates and Drosophila, while 1C11 lacks primate reactivity .
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Cell surface vs. nuclear detection: mAb14 distinguishes cancer-specific membrane PCNA from nuclear PCNA .
Product Specs
Target Background
This PCNA monoclonal antibody targets proliferating cell nuclear antigen (PCNA), an auxiliary protein for DNA polymerase delta. PCNA plays a crucial role in regulating eukaryotic DNA replication by enhancing polymerase processivity during leading strand elongation. It significantly stimulates the 3'-5' exonuclease and 3'-phosphodiesterase activities of APEX2, but not its apurinic-apyrimidinic (AP) endonuclease activity. Stimulation of APEX2 activity requires PCNA to be pre-loaded onto DNA. PCNA is essential for the DNA damage response (DDR), strategically positioned at the replication fork to coordinate DNA replication with DNA repair and DNA damage tolerance pathways. It functions as a scaffold, recruiting DDR proteins to facilitate DNA replication completion post-damage and promote post-replication repair. Monoubiquitinated PCNA recruits translesion synthesis (TLS) polymerases, while Lys-63-linked polyubiquitination of PCNA is involved in error-free pathways utilizing recombination mechanisms for lesion bypass.
- PCNA recognizes DNA structure via basic residues within its ring channel, interacting with consecutive DNA phosphates. PMID: 28071730
- HECW2 interacts with PCNA, mediating its ubiquitination and proteasomal degradation. PMID: 29753763
- SUMO2 conjugation, but not SUMO1 or SUMO3, to PCNA is induced on transcribed chromatin by the RNAPII-bound helicase RECQ5. PMID: 30006506
- Key PCNA-peptide interactions crucial for complex formation have been identified through simulation studies. Calculated binding energies correlate well with measured binding affinities. PMID: 29095607
- CDK-mediated phosphorylation of Cdt2 inactivates its ubiquitin ligase activity by reducing its PCNA affinity, regulating cell cycle protein levels. PMID: 29424068
- High CHAF1A and PCNA expression in cervical squamous cell carcinoma correlates with malignancy. PMID: 29382432
- The DDB2-PCNA interaction contributes to a proper DNA damage response for maintaining genome integrity. PMID: 29604309
- Cytoplasmic PCNA links glycolysis and cell survival in acute myeloid leukemia. PMID: 27759041
- PCNA is predominantly cytoplasmic, while hAng is nuclear and cytoplasmic; they colocalize in the cytoplasm, suggesting interaction. PMID: 28777577
- PCNA and E-cadherin may influence the prognosis of gastric cancer patients. PMID: 28611525
- PCNA and MutLalpha interact weakly to form a 1:1 complex dependent on PCNA interaction with MutLalpha PMS2 subunit's C-terminal endonuclease domain. PMID: 28439008
- FAN1 interaction with ubiquitinated PCNA alleviates replication stress and preserves genomic integrity independently of BRCA2. PMID: 29051491
- Matrine reduces PCNA and eIF4E expression, inhibiting A549 cell migration and proliferation, potentially via p53 and p21 upregulation. PMID: 28447756
- The highly regulated PCNA inner surface controls DNA damage resistance, offering opportunities for manipulating the DDR in cancer treatment. (Review) PMID: 28814116
- In embryonic stem cells, IGF1R interacts with and phosphorylates PCNA at tyrosine residues 60, 133, and 250, followed by mono- and polyubiquitination by RAD18 and SHPRH. PMID: 28924044
- The structure of the PCNA-UHRF2 peptide complex (residues 784-800) reveals the molecular basis for UHRF2 recognition via its PIP box. PMID: 28951215
- The p15PAF-PCNA complex is low-affinity and transient; its structure and dynamics were characterized using SAXS and molecular modeling. PMID: 28180305
- Dynamic binding of PARG's non-canonical PIP-box to PCNA. PMID: 28934471
- PCNA expression correlates with clinical stage, histological grade, and poor prognosis in osteosarcoma. PMID: 29019895
- A mechanism for progerin-induced genome instability and accelerated replicative senescence in Hutchinson-Gilford progeria syndrome is proposed. PMID: 28515154
- High PCNA expression is associated with lung adenocarcinoma. PMID: 28423618
- Eco1-mediated acetylation regulates PCNA sliding on DNA in the presence of damage, favoring homologous recombination linked to sister-chromatid cohesion. PMID: 27916662
- Mammalian damage-induced fork reversal requires PCNA ubiquitination, UBC13, K63-linked polyubiquitin chains, and ZRANB3, implicating ZRANB3 in error-free DNA damage tolerance. PMID: 28886337
- PCNA is central to faithful eukaryotic genome duplication and integrity. (Review) PMID: 28157503
- The human CTF18-RFC clamp-loader complex loads the PCNA sliding clamp with non-synthesizing POLE. PMID: 28199690
- The UNG2 N-terminus may tether PCNA and RPA at the replication fork; modifications disrupt complex formation. PMID: 28746850
- ECRG2 with cisplatin inhibits viability and induces apoptosis in esophageal cancer DDP-resistant cells, potentially via p53 upregulation and PCNA downregulation. PMID: 28348485
- Reduced PCNA(S228I) affinity for client proteins causes cellular defects contributing to PCNA-associated DNA repair disorder (PARD). PMID: 28073635
- RPA restricts PCNA to the upstream duplex region during DNA synthesis by blocking PCNA diffusion along ssDNA. PMID: 28590137
- POLH interaction with PCNA is crucial for pol-eta recruitment to UV-induced cyclobutane pyrimidine dimers for translesion synthesis (TLS); pol-eta dissociation is essential for high-fidelity replication. PMID: 26988343
- PCNA is a substrate of the HSV-1 deubiquitinase UL36USP, involved in virus uptake and maturation. PMID: 28348081
- Disruption of PCNA-lamins A/C interactions by prelamin A induces DNA replication fork stalling. PMID: 27676213
- PCNA prevents CAG repeat expansions by modulating DNA structures with base excision repair enzymes. PMID: 27793507
- Replication protein A binds tightly to ssDNA at blocked primer/template junctions and restricts PCNA to the upstream duplex. PMID: 28177605
- Determinants of PIP box for PCNA binding are discussed. PMID: 27084448
- CRL4CDT2 protects genomic integrity against replication stress via regulated proteolysis of PCNA-associated SDE2. PMID: 27906959
- Immunoexpression of Ki67, p53, MCM3, and PCNA in dental follicle epithelial remnants of impacted teeth and their correlation in dentigerous cysts and keratocystic odontogenic tumors are analyzed. PMID: 27516012
- REV1 promotes PCNA monoubiquitination after UV radiation via interaction with ubiquitinated RAD18. PMID: 26795561
- USP7 suppresses H2O2-induced mutagenesis through cell-cycle-independent DNA repair processes. PMID: 26673319
- Fenugreek seed extract (FCE) induced apoptosis and altered PCNA and p53 expression in HepG2 cells. PMID: 26557712
- The structure of the disease-causing S228I variant shows a conformational change affecting PCNA client protein binding. PMID: 26688547
- Armt1 regulates the DNA damage response via O-methylation of PCNA glutamyl residues. PMID: 26450907
- PCNA's hydrophobic pocket mediates ALKBH2 interaction; their association increases during replication. PMID: 26408825
- PCNA expression in giant cell tumor of bones is reported. PMID: 26339416
- p15PAF regulates PCNA sliding and facilitates the polymerase switch from replicative to translesion synthesis. PMID: 25762514
- 14-3-3zeta reduces DNA damage by stabilizing PCNA. PMID: 25169136
- IncRNA-PCNA-AS1 may be involved in gastric cancer development and serve as a biomarker. PMID: 26731993
- Bub1-LANA complex recruits PCNA to regulate Kaposi's sarcoma-associated herpesvirus latent replication and TLS. PMID: 26223641
- PCNA lysine K164 mutation disrupts mono-ubiquitination and DNA damage tolerance. PMID: 25692884
- A reverse PIP Box interaction with PCNA involves allosteric effects. PMID: 25036435
