E3 ubiquitin-protein ligase SIAH1 (SIAH1) (SIAH1)

E3 ubiquitin-protein ligase SIAH1 (SIAH1) is a member of the Seven in absentia homolog family, characterized by an N-terminal RING finger domain that confers E3 ligase activity. It plays a pivotal role in the ubiquitin-proteasome system by targeting a wide array of substrates—including beta-catenin, DCC, and alpha-synuclein—for degradation (UniProt Q8IUQ4). SIAH1 is deeply involved in regulating cellular processes such as apoptosis, DNA damage response, and hypoxia signaling (PubMed: 15103331). In oncology, it frequently functions as a tumor suppressor by downregulating pro-proliferative signaling pathways, though its depletion or overexpression is linked to various malignancies (PubMed: 11585923). Furthermore, SIAH1 is implicated in neurodegeneration, specifically in the pathogenesis of Parkinson's disease, where it promotes the ubiquitination and aggregation of alpha-synuclein (PubMed: 15630441). Therapeutic interest in SIAH1 focuses on its potential as a target for small molecule inhibitors or as a component in targeted protein degradation strategies.

Other names

Seven in absentia homolog 1Siah-1HUMSIAHSiah-1aSiah-1 protein

E3 ubiquitin ligase activity facilitating the transfer of ubiquitin from an E2 enzyme to specific substrate proteins, marking them for 26S proteasomal degradation.