CUL4 Antibody

Structure and Function of CUL4 Proteins

CUL4A and CUL4B share 83% sequence identity but exhibit distinct subcellular localization and functional roles :

• CUL4A: Localizes to both the nucleus and cytoplasm, forming the CRL4A complex with DDB1 and ROC1. It recruits substrates via WD40-repeat proteins (DCAFs) for ubiquitination .

• CUL4B: Primarily nuclear, facilitating DDB1 nuclear import independently of DDB2 .

Both proteins are neddylated for activation and interact with COP9 signalosome (CSN) and CAND1 to regulate substrate specificity .

Research Applications of CUL4 Antibodies

CUL4 antibodies are indispensable in studying their roles in disease mechanisms. Key applications include:

Cancer Biology

• Breast Cancer:

  • High CUL4A expression correlates with distant metastasis and epithelial-mesenchymal transition (EMT) via ZEB1 upregulation .

  • CUL4A silencing reduces tumor growth and proliferation in basal-like breast cancer models .

• Lung Cancer:

  CUL4 Expression	Clinical Correlation
  High CUL4A/CUL4B	Poor prognosis in NSCLC; associated with advanced T/N stage and metastasis .
  CUL4A knockdown	G1 arrest via p21 stabilization; CUL4B knockdown induces apoptosis via FOXO3A .

• Gastric and Ovarian Cancers:
  CUL4A overexpression promotes proliferation and chemoresistance .

Viral Pathogenesis

• HIV-1 Vpr protein hijacks CRL4 complexes to induce G2/M arrest, facilitating viral replication .

Therapeutic Implications

• Targeting CRL4 Complexes:

  • Inhibiting CUL4A/B neddylation or substrate binding disrupts oncogenic signaling .

  • Small-molecule inhibitors (e.g., MLN4924) block CRL4 activity, showing efficacy in preclinical models .

Challenges and Future Directions

• Specificity Issues: Cross-reactivity between CUL4A/B antibodies necessitates rigorous validation .

• Therapeutic Development: CRL4 inhibitors face challenges in balancing efficacy and toxicity due to broad substrate roles .