ASCC1 Antibody

Cell Line Reactivity

Western Blot Performance

Role in Bone Fragility and SMABF2

• ASCC1 mutations cause spinal muscular atrophy with congenital bone fractures-2 (SMABF2), characterized by severe hypotonia, gracile bones, and fractures .

• Mechanism:

  • Loss of ASCC1 disrupts osteoblast differentiation in mesenchymal stromal cells (hMSCs), reducing mineralization by 60% .

  • Upregulates adipogenesis (lipid droplet formation increases 3-fold) while downregulating RUNX2 (osteoblastogenesis master regulator) and SERPINF1 (osteoblast/adipocyte differentiation) .

  • Inhibits TGF-β/SMAD signaling, critical for bone development .

DNA Repair and Alkylation Damage Response

• ASCC1 coordinates the ALKBH3–ASCC complex to resolve alkylation damage (e.g., methyl methanesulfonate, MMS) .

• Key observations:

  • ASCC1 knockout increases ASCC3 foci formation by 40% but reduces ASCC2 colocalization by 33% .

  • The RNA ligase-like domain in ASCC1’s C-terminus modulates nuclear speckle dynamics during damage .

  • ASCC1 loss sensitizes cells to MMS, with survival rates dropping 50% compared to wild-type .

Transcriptional Regulation

• Acts as a coactivator for AP-1 and NF-κB transcription factors, influencing osteoblastogenesis and inflammatory pathways .

• Modulates TNFRSF11B (osteoprotegerin) and RASSF2 (tumor suppressor) expression .

Applications in Biomedical Research

1. SMABF2 Pathogenesis Studies:

   • Bone histomorphometry reveals low trabecular volume (−70%) and high marrow adiposity (+200%) in ASCC1-deficient patients .

2. DNA Repair Pathways:

   • Identifies RNA-binding motifs’ role in alkylation damage resolution .

3. Cancer Research:

   • Prostate cancer (PC-3) models show ASCC1/ASCC3 epistasis in MMS resistance .