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Siah1 in cancer and nervous system diseases (Review)
Hui Zhang1, Jie Wang1, Yidong Ge1
1Department of Oncology, The Affiliated Hospital of School of Medicine, Ningbo University, Ningbo, Zhejiang 315020, P.R. China.
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.
Insights
The ubiquitin-proteasome system regulates protein levels, and its dysregulation causes disease. Seven in absentia homolog 1 (Siah1) is an E3 ubiquitin ligase with crucial roles in cancer and nervous system diseases.
Area of Science:
- Biochemistry
- Molecular Biology
- Cellular Biology
Background:
- The ubiquitin-proteasome system (UPS) is critical for protein homeostasis; its dysregulation leads to disease.
- Seven in absentia homolog 1 (Siah1) is an E3 ubiquitin ligase involved in various physiological and pathological processes.
- Siah1's diverse roles, including in cancer and nervous system diseases, are influenced by its substrates and cellular context.
Purpose of the Study:
- To review the functions and regulations of Siah1.
- To highlight novel Siah1 substrates in cancer and nervous system diseases.
- To provide insights for future research and targeted therapies involving Siah1.
Main Methods:
- Literature review of Siah1 functions and regulations.
- Analysis of recent studies on Siah1 substrates.
- Focus on Siah1's role in cancer and nervous system disease pathogenesis.
Main Results:
- Siah1 exhibits context-dependent roles (promoter or suppressor) in diseases.
- Cellular microenvironment and subcellular localization modulate Siah1 activity.
- Novel Siah1 substrates have been identified, expanding our understanding of its regulatory network.
Conclusions:
- Understanding Siah1's molecular mechanisms is vital for deciphering signaling pathways.
- Siah1 presents a promising target for therapeutic strategies in cancer and neurological disorders.
- Further research into Siah1 substrates and regulation will advance clinical applications.
