Siah1 in cancer and nervous system diseases (Review)

Abstract

The dysregulation of the ubiquitin‑proteasome system will result in the abnormal accumulation and dysfunction of proteins, thus leading to severe diseases. Seven in absentia homolog 1 (Siah1), an E3 ubiquitin ligase, has attracted wide attention due to its varied functions in physiological and pathological conditions, and the numerous newly discovered Siah1 substrates. In cancer and nervous system diseases, the functions of Siah1 as a promoter or a suppressor of diseases are related to the change in cellular microenvironment and subcellular localization. At the same time, complex upstream regulations make Siah1 different from other E3 ubiquitin ligases. Understanding the molecular mechanism of Siah1 will help the study of various signaling pathways and benefit the therapeutic strategy of human diseases (e.g., cancer and nervous system diseases). In the present review, the functions and regulations of Siah1 are described. Moreover, novel substrates of Siah1 discovered in recent studies will be highlighted in cancer and nervous system diseases, providing ideas for future research and clinical targeted therapies using Siah1.

Keywords: E3 ubiquitin ligase; Siah1; cancer; nervous system diseases; tumor suppressor; ubiquitin‑proteasome system.