Catalogue

Background
Seven in absentia homolog 1 (SIAH-1) is a member of the RING-finger-containing E3 ubiquitin ligases. Alpha-synuclein and synphilin-1 are substrates of SIAH-1. Both proteins are involved in the development of Parkinson's disease (PD). Mutations in Parkin, another E3 ubiquitin ligase which ubiquinates synphilin-1 and glycosylated alpha-synuclein, have been defined as a major cause of autosomal recessive PD. The role of SIAH-1 in PD is highlighted by the fact that SIAH-1 is a component of the Lewy bodies and plays a role in apoptosis caused by nitric oxide (NO) induced oxidative stress. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) a classic glycolytic enzyme, and multi-functional protein. GAPDH plays role as a mediator for cell death. GAPDH translocates to the nucleus under a variety of stressors/conditions, most of which are associated with oxidative stress. Sequential steps lead to nuclear translocation of GAPDH during cell death; 1] a catalytic cysteine in GAPDH (C150 in rat GAPDH) is S-nitrosylated by nitric oxide (NO) which is generated from inducible nitric oxide synthase (iNOS) and/or neuronal NOS (nNOS); 2] the modified GAPDH becomes capable of binding with Siah1, an E3 ubiquitin ligase, and stabilizes it;3] the GAPDH-Siah protein complex translocates to the nucleus, dependent on Siah1's nuclear localization signal, and degrades Siah1's substrates in the nucleus, which results in cytotoxicity.

Synonyms: SIAH1 (seven in absentia homolog 1), E3 Ubiquitin Ligase

Source

Immunogen: Synthetic peptide derived from the human SIAH-1 protein.

Product

Product Form: Unconjugated

Formulation: Provided as solution in phosphate buffered saline with 0.08% sodium azide

Purification Method: Ammonium Sulfate Precipitation

Concentration: See vial for concentration

Applications
Antibody can be used for Western blotting (1-5 µg/ml). Optimal concentration should be evaluated by serial dilutions.

Functional Analysis: Western Blotting

Positive Control: Antibody tested on human brain lysate

Storage
Product should be stored at -20°C. Aliquot to avoid freeze/thaw cycles

Product Stability: See expiration date on vial

Shipping Conditions: Ship at ambient temperature, freeze upon arrival

Caution
This product is intended FOR RESEARCH USE ONLY, and FOR TESTS IN VITRO, not for use in diagnostic or therapeutic procedures involving humans or animals. It may contain hazardous ingredients. Please refer to the Safety Data Sheets (SDS) for additional information and proper handling procedures. Dispose product remainders according to local regulations.This datasheet is as accurate as reasonably achievable, but our company accepts no liability for any inaccuracies or omissions in this information.

References
1: Hu G., et al.; Mammalian homologs of seven in absentia regulate DCC via the ubiquitin-proteasome pathway.; Genes Dev. 11:2701-2714(1997). 2: Matsuzawa S., et al.; p53-inducible human homologue of Drosophila seven in absentia (Siah) inhibits cell growth: suppression by BAG-1.; EMBO J. 17:2736-2747(1998). 3: Hu G., Fearon E.R.; Siah-1 N-terminal RING domain is required for proteolysis function, and C-terminal sequences regulate oligomerization and binding to target proteins.; Mol. Cell. Biol. 19:724-732(1999). 4: Germani A., et al.; SIAH-1 interacts with alpha-tubulin and degrades the kinesin Kid by the proteasome pathway during mitosis.; Oncogene 19:5997-6006(2000). 5: Tanikawa J., et al.; p53 suppresses the c-Myb-induced activation of heat shock transcription factor 3.; J. Biol. Chem. 275:15578-15585(2000). 6: Matsuzawa S., Reed J.C.; Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses.; Mol. Cell 7:915-926(2001). 7: Liu J., et al. Siah-1 mediates a novel beta-catenin degradation pathway linking p53 to the adenomatous polyposis coli protein.; Mol. Cell 7:927-936(2001). 8: Tiedt R., et al.; The RING finger protein Siah-1 regulates the level of the transcriptional coactivator OBF-1.; EMBO J. 20:4143-4152(2001). 9: Boehm J., et al.; Regulation of BOB.1/OBF.1 stability by SIAH.; EMBO J. 20:4153-4162(2001). 10: Susini L., et al.; Siah-1 binds and regulates the function of Numb. Proc. Natl. Acad. Sci. U.S.A. 98:15067-15072(2001).

Protein Reference(s)

Database Name: UniProt

Accession Number: Q8IUQ4

Species Accession: Human

Safety Datasheet(s) for this product: