Recombinant Rat Gamma-secretase subunit PEN-2 (Psenen)
Description
Production and Expression Systems
Recombinant PEN-2 is produced via heterologous expression systems optimized for structural and functional fidelity:
E. coli-expressed PEN-2 is most common due to high yield and cost-effectiveness, though mammalian systems enable native-like folding for functional assays .
Applications in Research
Recombinant PEN-2 is pivotal in elucidating γ-secretase mechanisms and disease pathology:
Alzheimer’s Disease Models
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APP Processing: PEN-2 modulates Aβ42/Aβ40 ratios, a therapeutic target in AD .
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γ-Secretase Inhibitors: Recombinant PEN-2 aids in testing inhibitors like DAPT and BMS 299897 .
Notch Signaling Studies
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Pathway Activation: PEN-2-deficient cells show impaired Notch cleavage, linking γ-secretase dysfunction to developmental disorders .
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Drug Development: Selective γ-secretase modulators (GSMs) spare Notch signaling, reducing off-target effects .
Mutational Impact on γ-Secretase Function
| Mutation | Region | Effect on PS1 Endoproteolysis | Effect on Activity |
|---|---|---|---|
| N33A | TMD1 (N-terminal) | ↓ (Reduced) | ↓ (↓ Activity) |
| I53A | Loop | ↓ (↓ Stability) | ↓ (↓ Activity) |
| D90A/F94A | C-Terminal | – (No effect) | ↓ (↓ Stability) |
Data synthesized from systematic mutagenesis studies .
PEN-2’s Role in γ-Secretase Activation
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PS1 Endoproteolysis: PEN-2 triggers PS1 cleavage, generating active N- and C-terminal fragments .
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Complex Stabilization: The C-terminal domain prevents proteasomal degradation of PS fragments .
Clinical and Therapeutic Implications
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Alzheimer’s Therapeutics: PEN-2’s role in Aβ42/Aβ40 modulation positions it as a target for GSMs .
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Cancer Research: γ-Secretase inhibitors (e.g., BMS 299897) target Notch signaling in oncogenesis .
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Rare Diseases: PSENEN haploinsufficiency causes familial acne inversa (ACNINV2), linking γ-secretase to skin pathology .
Product Specs
Note: We prioritize shipping the format currently in stock. However, if you require a specific format, please indicate your preference in the order notes. We will fulfill your request based on availability.
Note: All our proteins are shipped with standard blue ice packs. If you require dry ice shipping, please inform us in advance, as additional charges will apply.
Target Background
- These findings indicate that functional mature islet-like clusters can be generated through the differentiation of pancreatic precursor cell aggregates within poly(ethylene glycol)-based hydrogel cultures. PMID: 20236034
- Nicastrin, presenilin 1, APH-1, and PEN-2 form an active gamma-secretase complex that is expressed in mitochondria. PMID: 15456764
