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.
Positive Control: Antibody tested on human brain lysate.
Immunogen: Synthetic peptide derived from the human SIAH-1 protein.
Purification Method: Antigen Immunoaffiinity Purification.
Formulation: Provided as ligand affinity purified antibody in phosphate buffered saline with 0.08% sodium azide.
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).
UniProt: Q8IUQ4.
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.
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