ran-4 Antibody

Key Antibodies Targeting Ran Proteins

Several well-characterized antibodies against Ran family proteins demonstrate distinct epitope recognition and functional impacts:

Functional Modulation of Nuclear Transport

• ARAN1 binds to the COOH-terminal domain of Ran only when complexed with importin β or related proteins (e.g., transportin, CAS). This interaction exposes the acidic epitope (-DEDDDL), enabling antibody binding and subsequent inhibition of RanBP1 recruitment .

• Consequence: Nuclear injection of ARAN1 disrupts SV-40 T-antigen import, confirming its role in blocking nuclear transport machinery .

Therapeutic Potential in Neurodegenerative Diseases

• α-GA 1 Antibody:

  • Reduces GA/GP/GR RAN protein aggregates in C9ORF72-linked ALS/FTD models by 45–61% after 37 weeks of treatment .

  • Mechanism: Enhances proteasomal activity by disassembling aggregates, enabling cross-clearance of multiple toxic proteins .

  • In vivo efficacy: Improved survival (32% increase) and reduced neuroinflammation in C9-BAC mice .

Performance Metrics

Critical Notes on Usage

• Denaturation Sensitivity: Anti-Ran-GTP antibodies (e.g., 26915) lose specificity in WB due to SDS-induced conformational changes .

• Epitope Stability: ARAN1 requires Ran-importin β complexes for binding, limiting utility in non-native conditions .

Future Directions

• Antibody Engineering: Humanized variants (e.g., α-GA 1) show promise for clinical translation in ALS/FTD .

• Multiplex Targeting: Simultaneous inhibition of RanBP2 and importin β could enhance nuclear transport blockade in cancer therapy .