PRKN as a Potential Drug Target: Unlocking the Potential of Parkin RBR E3 Ubiquitin Protein Ligase Transcript Variant 1

Target Name: PRKN

NCBI ID: G5071

PRKN

PRKN as a Potential Drug Target: Unlocking the Potential of Parkin RBR E3 Ubiquitin Protein Ligase Transcript Variant 1

Parkin RBR E3 ubiquitin protein ligase is a protein that plays a crucial role in the regulation of gene expression and protein degradation. Mutations in the Parkin gene have been associated with a range of neurological and psychiatric disorders, including Alzheimer's disease, Parkinson's disease, and various neurodegenerative conditions. The Parkin gene has also been implicated in the development of certain cancers. Therefore, targeting the Parkin gene has the potential to treat or prevent a variety of neurorological disorders.

PRKN as a Drug Target

The Parkin gene has several potential drug targets. One of these targets is PRKN, which is a transcript variant of the Parkin gene that has been shown to interact with various proteins, including Ku70 and ubiquitin. PRKN has been shown to regulate the stability and localization of ubiquitin, a protein that plays a critical role in the regulation of cellular processes and is involved in numerous cellular signaling pathways.

The interaction between PRKN and ubiquitin suggests that PRKN may be a potential drug target for diseases that are characterized by the accumulation of misfolded or misregulated ubiquitin. misfolded ubiquitin can have toxic effects on cells and contribute to the development of a variety of diseases, including neurodegenerative disorders.

PRKN as a Biomarker

Another potential use of PRKN as a drug target is its potential as a biomarker for certain diseases. The accumulation of misfolded ubiquitin can be detected in a variety of biological samples, including blood, urine, and brain tissue. Therefore, PRKN could be used as a biomarker for diseases such as Alzheimer's disease, Parkinson's disease, and various neurodegenerative conditions.

PRKN as a Therapeutic

Targeting PRKN as a drug target could potentially provide new therapeutic options for treating neurodegenerative disorders. By inhibiting the activity of PRKN, researchers could potentially reduce the production of misfolded ubiquitin and improve the stability and localization of ubiquitin in cells. This could lead to a variety of potential therapeutic effects, including the slowing of neurodegeneration and the regression of certain diseases.

Conclusion

In conclusion, PRKN is a transcript variant of the Parkin gene that has been shown to interact with various proteins, including Ku70 and ubiquitin. The interaction between PRKN and ubiquitin suggests that PRKN may be a potential drug target for diseases characterized by the accumulation of misfolded or misregulated ubiquitin. PRKN also has the potential as a biomarker for detecting certain diseases. Targeting PRKN as a drug target or biomarker could potentially provide new therapeutic options for treating neurodegenerative disorders. Further research is needed to fully understand the potential of PRKN as a drug target and biomarker.

Protein Name: Parkin RBR E3 Ubiquitin Protein Ligase

Functions: Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins (PubMed:10888878, PubMed:10973942, PubMed:11431533, PubMed:12150907, PubMed:12628165, PubMed:15105460, PubMed:16135753, PubMed:21376232, PubMed:21532592, PubMed:23754282, PubMed:23620051, PubMed:24660806, PubMed:24751536, PubMed:32047033, PubMed:29311685, PubMed:22396657). Substrates include SYT11 and VDAC1 (PubMed:32047033, PubMed:29311685). Other substrates are BCL2, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPTIN5, TOMM20, USP30, ZNF746, MIRO1 and AIMP2 (PubMed:10888878, PubMed:10973942, PubMed:11431533, PubMed:12150907, PubMed:12628165, PubMed:15105460, PubMed:16135753, PubMed:21376232, PubMed:21532592, PubMed:23754282, PubMed:23620051, PubMed:24660806, PubMed:24751536, PubMed:22396657). Mediates monoubiquitination as well as 'Lys-6', 'Lys-11', 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context (PubMed:19229105, PubMed:20889974, PubMed:25621951, PubMed:32047033, PubMed:25474007). Participates in the removal and/or detoxification of abnormally folded or damaged protein by mediating 'Lys-63'-linked polyubiquitination of misfolded proteins such as PARK7: 'Lys-63'-linked polyubiquitinated misfolded proteins are then recognized by HDAC6, leading to their recruitment to aggresomes, followed by degradation (PubMed:17846173, PubMed:19229105). Mediates 'Lys-63'-linked polyubiquitination of a 22 kDa O-linked glycosylated isoform of SNCAIP, possibly playing a role in Lewy-body formation (PubMed:11431533, PubMed:11590439, PubMed:15105460, PubMed:19229105, PubMed:15728840). Mediates monoubiquitination of BCL2, thereby acting as a positive regulator of autophagy (PubMed:20889974). Protects against mitochondrial dysfunction during cellular stress, by acting downstream of PINK1 to coordinate mitochondrial quality control mechanisms that remove and replace dysfunctional mitochondrial components (PubMed:32047033, PubMed:19029340, PubMed:19966284, PubMed:23620051, PubMed:24896179, PubMed:25527291, PubMed:18957282, PubMed:21376232, PubMed:22396657, PubMed:24660806, PubMed:25474007, PubMed:24784582, PubMed:11439185, PubMed:22082830, PubMed:23933751). Depending on the severity of mitochondrial damage and/or dysfunction, activity ranges from preventing apoptosis and stimulating mitochondrial biogenesis to regulating mitochondrial dynamics and eliminating severely damaged mitochondria via mitophagy (PubMed:32047033, PubMed:19029340, PubMed:19801972, PubMed:19966284, PubMed:23620051, PubMed:24896179, PubMed:25527291, PubMed:21376232, PubMed:22396657, PubMed:11439185, PubMed:22082830, PubMed:23933751, PubMed:33499712). Activation and recruitment onto the outer membrane of damaged/dysfunctional mitochondria (OMM) requires PINK1-mediated phosphorylation of both PRKN and ubiquitin (PubMed:24660806, PubMed:25474007, PubMed:24784582, PubMed:25527291). After mitochondrial damage, functions with PINK1 to mediate the decision between mitophagy or preventing apoptosis by inducing either the poly- or monoubiquitination of VDAC1, respectively; polyubiquitination of VDAC1 promotes mitophagy, while monoubiquitination of VDAC1 decreases mitochondrial calcium influx which ultimately inhibits apoptosis (PubMed:32047033). When cellular stress results in irreversible mitochondrial damage, promotes the autophagic degradation of dysfunctional depolarized mitochondria (mitophagy) by promoting the ubiquitination of mitochondrial proteins such as TOMM20, RHOT1/MIRO1, MFN1 and USP30 (PubMed:19029340, PubMed:19966284, PubMed:21753002, PubMed:23620051, PubMed:24896179, PubMed:25527291, PubMed:22396657, PubMed:23933751). Preferentially assembles 'Lys-6'-, 'Lys-11'- and 'Lys-63'-linked polyubiquitin chains, leading to mitophagy (PubMed:25621951, PubMed:32047033). The PINK1-PRKN pathway also promotes fission of damaged mitochondria by PINK1-mediated phosphorylation which promotes the PRKN-dependent degradation of mitochondrial proteins involved in fission such as MFN2 (PubMed:23620051). This prevents the refusion of unhealthy mitochondria with the mitochondrial network or initiates mitochondrial fragmentation facilitating their later engulfment by autophagosomes (PubMed:23620051). Regulates motility of damaged mitochondria via the ubiquitination and subsequent degradation of MIRO1 and MIRO2; in motor neurons, this likely inhibits mitochondrial intracellular anterograde transport along the axons which probably increases the chance of the mitochondria undergoing mitophagy in the soma (PubMed:22396657). Involved in mitochondrial biogenesis via the 'Lys-48'-linked polyubiquitination of transcriptional repressor ZNF746/PARIS which leads to its subsequent proteasomal degradation and allows activation of the transcription factor PPARGC1A (PubMed:21376232). Limits the production of reactive oxygen species (ROS) (PubMed:18541373). Regulates cyclin-E during neuronal apopto

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•   general information;
•   protein structure and compound binding;
•   protein biological mechanisms;
•   its importance;
•   the target screening and validation;
•   expression level;
•   disease relevance;
•   drug resistance;
•   related combination drugs;
•   pharmacochemistry experiments;
•   related patent analysis;
•   advantages and risks of development, etc.
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