Unlocking the Potential of POLD3: A Promising Drug Target and Biomarker

Target Name: POLD3

NCBI ID: G10714

POLD3

Unlocking the Potential of POLD3: A Promising Drug Target and Biomarker

Protein phosphatase 1 (PP1) is an essential enzyme that regulates various cellular processes.PP1 is composed of two subunits, POLD1 and POLD2, which function together to catalyze the conversion of ATP to ADP and release of phosphate groups. POLD3, the regulatory subunit 128 of PP1, plays a crucial role in its function by regulating the activity of PP1. The dephosphorylation of ATP by PP1 is a critical process for maintaining cellular homeostasis, and POLD3 is involved in this process by regulating the rate of phosphorylation and dephosphorylation of the active site.

The discovery of POLD3 as a drug target and biomarker has significant implications for the development of new treatments for various diseases. In this article, we will explore the current understanding of POLD3 and its potential as a drug target and biomarker.

POLD3 as a Drug Target

POLD3 has been identified as a potential drug target due to its unique structure and its involvement in various cellular processes. POLD3 is a 128-kDa protein that contains a catalytic active site, a regulatory region, and a C-terminus. The catalytic active site is the site of the phosphoryl transfer, which is the rate-limiting step in the phosphorylation process. The regulatory region is responsible for regulating the activity of PP1, and the C-terminus is the site of the protein-protein interaction (PPI) with other cellular components.

Several studies have demonstrated that POLD3 can be targeted by small molecules. For instance, a series of inhibitors have been shown to inhibit the activity of POLD3 and prevent the phosphorylation of ATP. These inhibitors have been shown to have a range of effects on various cellular processes, including the regulation of cell growth, apoptosis, and protein synthesis.

In addition to its role as a drug target, POLD3 has also been shown to be a potential biomarker for various diseases. The phosphorylation of POLD3 is regulated by various factors, including temperature, pH, and the concentration of ATP. Therefore, the activity of POLD3 can be used as a sensitive indicator of cellular stress, which can be linked to the development of various diseases, such as cancer, neurodegenerative diseases, and metabolic disorders.

POLD3 as a Biomarker

POLD3 has also been used as a biomarker for various diseases. The phosphorylation of POLD3 is regulated by various factors, including temperature, pH, and the concentration of ATP. Therefore, the activity of POLD3 can be used as a sensitive indicator of cellular stress, which can be linked to the development of various diseases, such as cancer, neurodegenerative diseases, and metabolic disorders.

Studies have shown that the phosphorylation of POLD3 is affected by various stressors, including reactive oxygen species (ROS), reactive nitrogen species (RNS), and protein misfolding. ROS and RNS are highly reactive molecules that can damage cellular components, including POLD3. Prolonged exposure to these molecules can lead to the phosphorylation of POLD3 and its subsequent regulation of PP1.

In addition to its role as a biomarker, POLD3 has also been shown to play a role in the regulation of cellular processes. The phosphorylation of POLD3 is involved in the regulation of various cellular processes, including cell growth, apoptosis, and protein synthesis. Therefore, the activity of POLD3 can be used as an indicator of cellular function and its potential to serve as a drug target or biomarker.

Conclusion

In conclusion, POLD3 is a protein that plays a crucial role in the regulation of various cellular processes. Its catalytic active site is involved in the phosphorylation of ATP, and its regulatory region is responsible for regulating the activity of PP1. The phosphorylation of POLD3 can be used as a sensitive indicator of cellular stress and its potential to serve as a drug target or biomarker. Further research is needed to fully understand the role of POLD3 in cellular processes and its potential as a drug target or biomarker.

Protein Name: DNA Polymerase Delta 3, Accessory Subunit

Functions: Accessory component of both the DNA polymerase delta complex and the DNA polymerase zeta complex (PubMed:22801543, PubMed:17317665, PubMed:24449906). As a component of the trimeric and tetrameric DNA polymerase delta complexes (Pol-delta3 and Pol-delta4, respectively), plays a role in high fidelity genome replication, including in lagging strand synthesis, and repair. Required for optimal Pol-delta activity. Stabilizes the Pol-delta complex and plays a major role in Pol-delta stimulation by PCNA (PubMed:10219083, PubMed:10852724, PubMed:11595739, PubMed:16510448, PubMed:24035200). Pol-delta3 and Pol-delta4 are characterized by the absence or the presence of POLD4. They exhibit differences in catalytic activity. Most notably, Pol-delta3 shows higher proofreading activity than Pol-delta4 (PubMed:19074196, PubMed:20334433). Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may also be better suited to fulfill this task, exhibiting near-absence of strand displacement activity compared to Pol-delta4 and stalling on encounter with the 5'-blocking oligonucleotides. Pol-delta3 idling process may avoid the formation of a gap, while maintaining a nick that can be readily ligated (PubMed:24035200). Along with DNA polymerase kappa, DNA polymerase delta carries out approximately half of nucleotide excision repair (NER) synthesis following UV irradiation. In this context, POLD3, along with PCNA and RFC1-replication factor C complex, is required to recruit POLD1, the catalytic subunit of the polymerase delta complex, to DNA damage sites (PubMed:20227374). Under conditions of DNA replication stress, required for the repair of broken replication forks through break-induced replication (BIR) (PubMed:24310611). Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites performed by Pol-delta4, independently of DNA polymerase zeta (REV3L) or eta (POLH). Facilitates abasic site bypass by DNA polymerase delta by promoting extension from the nucleotide inserted opposite the lesion (PubMed:19074196, PubMed:25628356, PubMed:27185888). Also involved in TLS, as a component of the tetrametric DNA polymerase zeta complex. Along with POLD2, dramatically increases the efficiency and processivity of DNA synthesis of the DNA polymerase zeta complex compared to the minimal zeta complex, consisting of only REV3L and REV7 (PubMed:24449906)

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•   protein biological mechanisms;
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•   the target screening and validation;
•   expression level;
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The report is helpful for project application, drug molecule design, research progress updates, publication of research papers, patent applications, etc. If you are interested to get a full version of this report, please feel free to contact us at BD@silexon.ai

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