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Pinin, desmosome associated protein (PNN)
- Target
- PNN
- Molecular classification
- Other (moonlighting protein with dual location), RNA-binding protein, Component of the exon junction complex (EJC), Structural molecule (associates desmosome–intermediate filaments), Splicing factor complex, auxiliary component, Cell adhesion-associated protein
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Overview
Pinin, desmosome associated protein (PNN), is a multifunctional (moonlighting) nuclear and cytoplasmic protein originally identified at desmosome–intermediate filament junctions, but now recognized to also localize within nuclear speckles as part of the spliceosome and exon junction complex. It functions in RNA binding and pre-mRNA splicing, and upholds cell-cell adhesion and epithelial identity by regulating alternative splicing and interacting with transcriptional regulators like CtBP1/2. Disruption of pinin impairs cell adhesion, increases apoptosis, alters gene expression via changes in splicing, and sensitizes cells to chemotherapeutic agents such as Paclitaxel. While not itself a classic drug target, its overexpression correlates with certain tumors, and it is genetically required for epithelial cell survival and differentiation.
- Other names
- PNNPininDRS (Desmosome-related structural protein)DRS1
02
Mechanism of action
Not applicable; no drugs are known to directly target Pinin.
03
Biological functions
Cell-cell adhesionAlternative pre-mRNA splicingRNA bindingmRNA processingRegulation of E-cadherin gene expression and epithelial identityMaintenance of epithelial cell identity/differentiationParticipation in gene transcriptional regulation (by interaction with transcriptional repressors such as CtBP1/2)Potential tumor suppressor activity in certain cancers
04
Disease associations
Cancer (including ovarian tumors and renal cell carcinoma)Possibly involved in melanoma and rare metabolic disorders, as noted in OMIM and GeneCardsDevelopmental defects (disrupted pinin causes apoptosis and epithelial development issues in animal models)Other (rare genetic diseases like 3-Methylglutaconic Aciduria With Cataracts, Neurologic Involvement And Neutropenia)
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Safety considerations
Essential gene for epithelial cell survival and differentiation: Loss of function leads to apoptosis and tissue developmental defects in model organismsNo established therapeutic use; thus, safety concerns as a drug target are not characterized.
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Interacting drugs
Paclitaxel (knockdown of Pinin increases Paclitaxel sensitivity in ovarian cancer cells; however, Pinin itself is not a direct drug target)
07
Biomarkers
Pinin expression level (proposed as a biomarker for epithelial identity or tumor subtype in ovarian cancer, potentially predictive of chemoresponse)
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