E3 ubiquitin-protein ligase SIAH1 (SIAH1)

E3 ubiquitin-protein ligase SIAH1 (SIAH1) is a member of the seven in absentia homolog (SIAH) family and acts as a RING-type E3 ubiquitin ligase, catalyzing the transfer of ubiquitin to target proteins and marking them for proteasomal degradation[1][4][11]. SIAH1 plays pivotal roles in regulating the stability of diverse proteins involved in apoptosis, cell cycle control, DNA damage response, hypoxia response, and several signaling pathways such as Wnt/β-catenin, p53, and estrogen receptor signaling[2][4][6][7][9]. Functionally, SIAH1 has been implicated both as a tumor suppressor and, in specific contexts, an oncogene in several human cancers, and is involved in neurodegenerative diseases such as Parkinson’s disease[2][7]. The protein comprises an N-terminal RING domain (responsible for its E3 ligase catalytic activity), two zinc finger domains, and a substrate-binding domain, enabling interaction with a variety of substrates and co-factors[7][9]. SIAH1 is considered an attractive, albeit challenging, therapeutic target due to the wide spectrum of cellular roles and its context-dependent effects in different tissues and disease states[2][7].

Other names

Siah-1hSIAH1HUMSIAHSeven in absentia homolog 1Siah-1aBURHASSIAH1ARING-type E3 ubiquitin transferase SIAH1seven in absentia homolog 1siah-1a

Drugs would hypothetically act via inhibition or modulation of E3 ligase activity, consequently impacting the ubiquitination and degradation of SIAH1 substrates (such as β-catenin, Akt3, and others)[2][6][9].