Siah E3 Ubiquitin Protein Ligase 1, commonly referred to as Siah1, is a human homolog of the Drosophila seven in absentia (sina) gene. It is a member of the E3 ubiquitin ligase family, which plays a crucial role in the ubiquitination process, a post-translational modification that tags proteins for degradation by the proteasome .
Siah1 is encoded by the SIAH1 gene located on chromosome 16 in humans . The protein is involved in the ubiquitination and proteasome-mediated degradation of specific proteins. This activity is essential for various cellular processes, including cell cycle regulation, apoptosis, and response to hypoxia .
Siah1 has been implicated in several critical biological pathways and diseases. It acts as a tumor suppressor gene and plays a significant role in the development of malignant tumors, such as colorectal cancer (CRC). Studies have shown that downregulation of Siah1 promotes CRC cell proliferation and migration by regulating the ubiquitination and degradation of key signaling proteins like AKT and YAP .
Additionally, Siah1 is involved in the regulation of the cellular response to hypoxia and the induction of apoptosis. Its activity has also been linked to the development of certain forms of Parkinson’s disease .
The potential role of Siah1 in cancer progression and its involvement in critical signaling pathways make it a promising target for therapeutic interventions. Overexpression of Siah1 has been shown to inhibit CRC cell proliferation and invasion, suggesting its potential as a prognostic biomarker and therapeutic target in cancer treatment .
Moreover, understanding the molecular mechanisms of Siah1’s activity can provide insights into the development of novel therapeutic strategies for diseases associated with its dysregulation, such as Parkinson’s disease and other neurodegenerative disorders .