siah2l Antibody

Introduction to SIAH2 Antibody

SIAH2 antibodies are immunological reagents designed to detect and quantify the SIAH2 protein, a RING finger E3 ubiquitin ligase involved in ubiquitin-proteasome system (UPS) regulation. SIAH2 targets substrates such as PHD3, Sprouty2, and androgen receptor (AR) for degradation, influencing cellular processes like hypoxia adaptation, immune regulation, and cancer metastasis .

Validated Applications in Research:

• Western Blot (WB): Detected SIAH2 in mouse brain tissue and MCF-7 cells .

• Immunohistochemistry (IHC): Localized SIAH2 in tumor microenvironments and immune cells .

• Immunoprecipitation (IP): Used to study SIAH2 interactions with AR and substrates like Sprouty2 .

Role in Cancer Immunity

• Melanoma: Siah2^−/− mice exhibited reduced tumor growth and Treg infiltration due to SIAH2's regulation of p27-mediated cell cycle arrest in Tregs. This correlated with enhanced anti-PD-1 therapy efficacy .

• Prostate Cancer: Androgen deprivation therapy (ADT) increased SIAH2 activity, promoting AR degradation and castration-resistant progression. SIAH2 antibody studies revealed its stabilization by AR and role in CRPC development .

Mechanistic Insights

• Substrate Targeting: SIAH2 ubiquitinates PHD3 and Sprouty2, modulating HIF-1α stability and MAPK signaling .

• Auto-Regulation: SIAH2 undergoes self-ubiquitination, which is inhibited by AR, leading to protein stabilization .

Clinical and Therapeutic Implications

Future Directions

• Biomarker Potential: Low SIAH2 and FOXP3 expression in melanoma correlates with immune responsiveness, suggesting utility in patient stratification .

• Therapeutic Targeting: Developing SIAH2 inhibitors could enhance anti-tumor immunity by selectively modulating Treg activity .