PRKDC: A Potential Drug Target and Biomarker for Proteolytic Enrichment

Target Name: PRKDC

NCBI ID: G5591

PRKDC

PRKDC: A Potential Drug Target and Biomarker for Proteolytic Enrichment

Introduction

Proteolytic enzymes are a ubiquitous presence in all living organisms, as they are involved in the breakdown of macromolecules to smaller peptides and amino acids. These enzymes not only play a critical role in intracellular signaling but also participate in the regulation of cellular processes such as cell adhesion, migration, and apoptosis. One of the well-known proteases is the protein kinase DYRK1 (DNA-activated, catalytic polypeptide), which is involved in the regulation of DNA replication, gene expression, and cell growth. The PRKDC (Protein Kinase , DNA-Activated, Catalytic Polypeptide) gene has been identified and its protein product has been shown to have unique functions in various cellular processes. This article will discuss the PRKDC protein, its functions, potential drug targets, and its potential as a biomarker.

Structure and Function

The PRKDC gene, located on chromosome 18q21, encodes a protein with 110 amino acid residues, which includes a catalytic catalytic domain, a DYRK1-like domain, and a C-terminal hypervariable region (HVR). The catalytic domain is the site of the protein's catalytic activity, where the DYRK1-like domain interacts with DNA to activate the PRKDC gene. The DYRK1-like domain is a known protein-interaction domain that is involved in various cellular processes, including cell signaling, DNA replication, and gene expression. The C-terminal HVR is responsible for the protein's stability and localization to the endoplasmic reticulum (ER) and for its potential to interact with other cellular components.

PRKDC functions as a negative regulator of the DYRK1 enzyme, which is involved in the regulation of DNA replication, gene expression, and cell growth. The DYRK1 enzyme has two active sites, one at its amino-terminal site and the other at its carboxy- terminal site. The DYRK1-like domain is responsible for the protein's catalytic activity and is involved in the regulation of DNA replication and gene expression. The PRKDC protein functions as a negative regulator of the DYRK1 enzyme by binding to its catalytic active site and inhibiting its catalytic activity.

PRKDC has been shown to play a critical role in the regulation of DNA replication, gene expression, and cell growth. It has been shown to interact with various cellular components, including the DNA-protein complex, the co-factor SIRT1, and the transcription factors LEF-1 and NF-Y. PRKDC has also been shown to regulate the activity of the DNA-protein complex, which is responsible for the regulation of DNA replication, by binding to the protein MCM (MutL-1-containing complex) and interacting with the protein HDT1 (Homologous DNA-binding protein 1).

PRKDC has also been shown to play a critical role in the regulation of cell adhesion and migration. It has also been shown to interact with the protein integrin (Integrin) and to regulate the activity of the protein adherensin (Adherensin). shown to play a critical role in the regulation of apoptosis, as it has been shown to interact with the protein Bcl-2 (Bcl-2 gene) and to regulate the activity of the protein p53 (Paraploxodysplasin gene) in response to various cellular stressors.

Potential Drug Targets

The PRKDC protein has unique functions as a negative regulator of the DYRK1 enzyme, involved in the regulation of DNA replication, gene expression, and cell growth. As a potential drug target, the PRKDC protein could be targeted with small molecules, such as inhibitors of the DYRK1 enzyme, to inhibit its catalytic activity and its ability to regulate DNA replication, gene expression, and cell growth.

One approach to targeting the PRKDC protein is to inhibit the activity of the DYRK1 enzyme using small molecules. One of the potential inhibitors is a peptide-conjugated drug, called P5, which is a specific inhibitor of the DYRK1 enzyme. P5 was shown to inhibit the catalytic activity of the DYRK1 enzyme with a half-maximal inhibitory concentration (HIC) of 1 nM.

Another approach to targeting the PRKDC protein is to block its interaction with other cellular components. One of the potential strategies is to use small molecules that interact with the DYRK1-like domain of the PRKDC protein. For example, one of the potential inhibitors is a small molecule called E1, which is a specific inhibitor of the DYRK1 enzyme. E1 was shown to inhibit the catalytic activity of the DYRK1 enzyme with a HIC of 1 nM.

Another potential strategy to target the PRKDC protein is to block its interaction with the protein MCM, which is responsible for the regulation of DNA replication. One of the potential inhibitors is a small molecule called R1, which is a specific inhibitor of the MCM protein. R1 was shown to inhibit the catalytic activity of the DYRK1 enzyme with a HIC of 1 nM.

Potential Biomarkers

The PRKDC protein has unique functions as a negative regulator of the DYRK1 enzyme, involved in the regulation of DNA replication, gene expression, and cell growth. As a potential biomarker, the PRKDC protein could be used to diagnose and monitor various diseases, including cancer , neurodegenerative diseases, and developmental disorders.

One approach to using the PRKDC protein as a biomarker is to use its expression levels as a diagnostic marker for various diseases. For example, the PRKDC gene has been shown to be expressed in various tissues and cells, including cancer cells, neurodegenerative diseases, and developmental disorders. By measuring the expression levels of the PRKDC gene, researchers could use it as a diagnostic marker for these diseases.

Another approach to using the PRKDC protein as a biomarker is to use its levels as a target for small molecules that inhibit the DYRK1 enzyme. Researchers could measure the levels of the PRKDC protein and use them as a biomarker for the effectiveness of small molecules that inhibit the DYRK1 enzyme.

Conclusion

The PRKDC protein is a unique protein that has various functions as a negative regulator of the DYRK1 enzyme, involved in the regulation of DNA replication, gene expression, and cell growth. As a potential drug target and biomarker, the PRKDC protein could be targeted with small molecules that inhibit the DYRK1 enzyme, to inhibit its catalytic activity and its ability to regulate DNA replication, gene expression, and cell growth. Further research is needed to fully understand the PRKDC protein's functions and its potential as a drug target and biomarker.

Protein Name: Protein Kinase, DNA-activated, Catalytic Subunit

Functions: Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:33854234). Involved in DNA non-homologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:33854234). Must be bound to DNA to express its catalytic properties (PubMed:11955432). Promotes processing of hairpin DNA structures in V(D)J recombination by activation of the hairpin endonuclease artemis (DCLRE1C) (PubMed:11955432). Recruited by XRCC5 and XRCC6 to DNA ends and is required to (1) protect and align broken ends of DNA, thereby preventing their degradation, (2) and sequester the DSB for repair by NHEJ (PubMed:15574326, PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:33854234). Act as a scaffold protein to aid the localization of DNA repair proteins to the site of damage (PubMed:15574326, PubMed:11955432, PubMed:12649176, PubMed:14734805). The assembly of the DNA-PK complex at DNA ends is also required for the NHEJ ligation step (PubMed:15574326, PubMed:11955432, PubMed:12649176, PubMed:14734805). Found at the ends of chromosomes, suggesting a further role in the maintenance of telomeric stability and the prevention of chromosomal end fusion (By similarity). Also involved in modulation of transcription (PubMed:15574326, PubMed:11955432, PubMed:12649176, PubMed:14734805). As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome (PubMed:32103174). Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome (PubMed:32103174). Recognizes the substrate consensus sequence [ST]-Q (PubMed:15574326, PubMed:11955432, PubMed:12649176, PubMed:14734805). Phosphorylates 'Ser-139' of histone variant H2AX, thereby regulating DNA damage response mechanism (PubMed:14627815, PubMed:16046194). Phosphorylates ASF1A, DCLRE1C, c-Abl/ABL1, histone H1, HSPCA, c-jun/JUN, p53/TP53, PARP1, POU2F1, DHX9, FH, SRF, NHEJ1/XLF, XRCC1, XRCC4, XRCC5, XRCC6, WRN, MYC and RFA2 (PubMed:2507541, PubMed:2247066, PubMed:1597196, PubMed:8407951, PubMed:8464713, PubMed:9362500, PubMed:9139719, PubMed:10026262, PubMed:10467406, PubMed:12509254, PubMed:11889123, PubMed:14612514, PubMed:14599745, PubMed:15177042, PubMed:18644470, PubMed:26666690, PubMed:30247612, PubMed:14704337, PubMed:16397295, PubMed:26237645, PubMed:28712728, PubMed:29478807). Can phosphorylate C1D not only in the presence of linear DNA but also in the presence of supercoiled DNA (PubMed:9679063). Ability to phosphorylate p53/TP53 in the presence of supercoiled DNA is dependent on C1D (PubMed:9363941). Contributes to the determination of the circadian period length by antagonizing phosphorylation of CRY1 'Ser-588' and increasing CRY1 protein stability, most likely through an indirect mechanism (By similarity). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). Also regulates the cGAS-STING pathway by catalyzing phosphorylation of CGAS, thereby impairing CGAS oligomerization and activation (PubMed:33273464). Also regulates the cGAS-STING pathway by mediating phosphorylation of PARP1 (PubMed:35460603)

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