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Mouse Anti-PCNA Recombinant Antibody (CB327) (CBMAB-CS327LY)


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Summary

Host Animal
Mouse
Specificity
Human, Mouse, Rat
Clone
CB327
Antibody Isotype
IgG
Application
WB, IHC

Basic Information

Immunogen
KLH-conjugated synthetic peptide encompassing a sequence of human PCNA.
Specificity
Human, Mouse, Rat
Antibody Isotype
IgG
Clonality
Monoclonal
Application Notes
The COA includes recommended starting dilutions, optimal dilutions should be determined by the end user.

Formulations & Storage [For reference only, actual COA shall prevail!]

Format
Liquid
Buffer
30% glycerol
Preservative
0.01% sodium azide
Storage
Store at +4°C short term (1-2 weeks). Aliquot and store at -20°C long term. Avoid repeated freezethaw cycles.

Target

Full Name
Proliferating Cell Nuclear Antigen
Introduction
The protein encoded by this gene is found in the nucleus and is a cofactor of DNA polymerase delta. The encoded protein acts as a homotrimer and helps increase the processivity of leading strand synthesis during DNA replication. In response to DNA damage, this protein is ubiquitinated and is involved in the RAD6-dependent DNA repair pathway. Two transcript variants encoding the same protein have been found for this gene. Pseudogenes of this gene have been described on chromosome 4 and on the X chromosome. [provided by RefSeq, Jul 2008]
Entrez Gene ID
Human5111
Mouse18538
Rat25737
UniProt ID
HumanP12004
MouseP17918
RatP04961
Alternative Names
Proliferating cell nuclear antigen, Cyclin
Function
Auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand. Induces a robust stimulatory effect on the 3'-5' exonuclease and 3'-phosphodiesterase, but not apurinic-apyrimidinic (AP) endonuclease, APEX2 activities. Has to be loaded onto DNA in order to be able to stimulate APEX2. Plays a key role in DNA damage response (DDR) by being conveniently positioned at the replication fork to coordinate DNA replication with DNA repair and DNA damage tolerance pathways (PubMed:24939902).
Acts as a loading platform to recruit DDR proteins that allow completion of DNA replication after DNA damage and promote postreplication repair: Monoubiquitinated PCNA leads to recruitment of translesion (TLS) polymerases, while 'Lys-63'-linked polyubiquitination of PCNA is involved in error-free pathway and employs recombination mechanisms to synthesize across the lesion (PubMed:24695737).
Biological Process
Base-excision repair, gap-fillingIEA:Ensembl
Cellular response to hydrogen peroxideIEA:Ensembl
Cellular response to UVManual Assertion Based On ExperimentIDA:UniProtKB
Cellular response to xenobiotic stimulusIEA:Ensembl
Epithelial cell differentiationManual Assertion Based On ExperimentIEP:UniProtKB
Estrous cycleIEA:Ensembl
Heart developmentIEA:Ensembl
Leading strand elongationManual Assertion Based On ExperimentIBA:GO_Central
Liver regenerationIEA:Ensembl
Mismatch repairManual Assertion Based On ExperimentIDA:BHF-UCL
Mitotic telomere maintenance via semi-conservative replicationBy SimilarityISS:BHF-UCL
Negative regulation of transcription by RNA polymerase IIIEA:Ensembl
Positive regulation of deoxyribonuclease activityManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of DNA repairManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of DNA replicationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of DNA-directed DNA polymerase activityManual Assertion Based On ExperimentIMP:UniProtKB
Replication fork processingBy SimilarityISS:BHF-UCL
Response to cadmium ionIEA:Ensembl
Response to dexamethasoneIEA:Ensembl
Response to estradiolIEA:Ensembl
Response to L-glutamateIEA:Ensembl
Translesion synthesisManual Assertion Based On ExperimentIDA:UniProtKB
Cellular Location
Nucleus
Colocalizes with CREBBP, EP300 and POLD1 to sites of DNA damage (PubMed:24939902).
Forms nuclear foci representing sites of ongoing DNA replication and vary in morphology and number during S phase (PubMed:15543136).
Co-localizes with SMARCA5/SNF2H and BAZ1B/WSTF at replication foci during S phase (PubMed:15543136).
Together with APEX2, is redistributed in discrete nuclear foci in presence of oxidative DNA damaging agents.
Involvement in disease
Ataxia-telangiectasia-like disorder 2 (ATLD2):
A neurodegenerative disorder due to defects in DNA excision repair. ATLD2 is characterized by developmental delay, ataxia, sensorineural hearing loss, short stature, cutaneous and ocular telangiectasia, and photosensitivity.
PTM
Phosphorylated. Phosphorylation at Tyr-211 by EGFR stabilizes chromatin-associated PCNA.
Acetylated by CREBBP and p300/EP300; preferentially acetylated by CREBBP on Lys-80, Lys-13 and Lys-14 and on Lys-77 by p300/EP300 upon loading on chromatin in response to UV irradiation (PubMed:24939902, PubMed:19419956).
Lysine acetylation disrupts association with chromatin, hence promoting PCNA ubiquitination and proteasomal degradation in response to UV damage in a CREBBP- and EP300-dependent manner (PubMed:24939902).
Acetylation disrupts interaction with NUDT15 and promotes degradation (PubMed:19419956).
Ubiquitinated (PubMed:24939902, PubMed:20227374).
Following DNA damage, can be either monoubiquitinated to stimulate direct bypass of DNA lesions by specialized DNA polymerases or polyubiquitinated to promote recombination-dependent DNA synthesis across DNA lesions by template switching mechanisms. Following induction of replication stress, monoubiquitinated by the UBE2B-RAD18 complex on Lys-164, leading to recruit translesion (TLS) polymerases, which are able to synthesize across DNA lesions in a potentially error-prone manner. An error-free pathway also exists and requires non-canonical polyubiquitination on Lys-164 through 'Lys-63' linkage of ubiquitin moieties by the E2 complex UBE2N-UBE2V2 and the E3 ligases, HLTF, RNF8 and SHPRH. This error-free pathway, also known as template switching, employs recombination mechanisms to synthesize across the lesion, using as a template the undamaged, newly synthesized strand of the sister chromatid. Monoubiquitination at Lys-164 also takes place in undamaged proliferating cells, and is mediated by the DCX(DTL) complex, leading to enhance PCNA-dependent translesion DNA synthesis. Sumoylated during S phase.
Methylated on glutamate residues by ARMT1/C6orf211.
More Infomation

Bhardwaj, V. K., & Purohit, R. (2022). A lesson for the maestro of the replication fork: targeting the protein‐binding interface of proliferating cell nuclear antigen for anticancer therapy. Journal of Cellular Biochemistry, 123(6), 1091-1102.

Yu, S., Qiao, X., Song, X., Yang, Y., Zhang, D., Sun, W., ... & Song, L. (2022). The proliferating cell nuclear antigen (PCNA) is a potential proliferative marker in oyster Crassostrea gigas. Fish & Shellfish Immunology, 122, 306-315.

Liu, R., Sun, K., Wang, Y., Jiang, Y., Kang, J., & Ma, H. (2021). The effects of proliferating cell nuclear antigen and p53 in patients with oral squamous cell carcinoma: a systematic review and meta-analysis. Annals of translational medicine, 9(23).

Lim, S., Khoo, R., Peh, K. M., Teo, J., Chang, S. C., Ng, S., ... & Partridge, A. W. (2020). bioPROTACs as versatile modulators of intracellular therapeutic targets including proliferating cell nuclear antigen (PCNA). Proceedings of the National Academy of Sciences, 117(11), 5791-5800.

Cardano, M., Tribioli, C., & Prosperi, E. (2020). Targeting proliferating cell nuclear antigen (PCNA) as an effective strategy to inhibit tumor cell proliferation. Current cancer drug targets, 20(4), 240-252.

Mathews, M. B. (2020). The proliferating cell nuclear antigen, PCNA, a cell growth-regulated DNA replication factor. In Growth control during cell aging (pp. 89-120). CRC Press.

Ye, X., Ling, B., Xu, H., Li, G., Zhao, X., Xu, J., ... & Liu, L. (2020). Clinical significance of high expression of proliferating cell nuclear antigen in non-small cell lung cancer. Medicine, 99(16), e19755.

Lu, E. M. C., Ratnayake, J., & Rich, A. M. (2019). Assessment of proliferating cell nuclear antigen (PCNA) expression at the invading front of oral squamous cell carcinoma. BMC oral health, 19, 1-7.

Gonzalez-Magaña, A., De Opakua, A. I., Romano-Moreno, M., Murciano-Calles, J., Merino, N., Luque, I., ... & De Biasio, A. (2019). The p12 subunit of human polymerase δ uses an atypical PIP box for molecular recognition of proliferating cell nuclear antigen (PCNA). Journal of biological chemistry, 294(11), 3947-3956.

Peng, B., Ortega, J., Gu, L., Chang, Z., & Li, G. M. (2019). Phosphorylation of proliferating cell nuclear antigen promotes cancer progression by activating the ATM/Akt/GSK3β/Snail signaling pathway. Journal of Biological Chemistry, 294(17), 7037-7045.

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For research use only. Not intended for any clinical use.

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