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Published on: June 21, 2021
Transcriptional regulation via cysteine thiol modification: a novel molecular strategy for chemoprevention and
Hye-Kyung Na1, Young-Joon Surh
1National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Seoul, South Korea.
Abstract:
Chemoprevention refers to the use of defined nontoxic chemical regimens to inhibit, reverse, or retard the process of multistage carcinogenesis that involves multiple signal transduction events. Identification of signaling molecules associated with carcinogenesis as prime targets of chemopreventive agents has become an area of great interest. Recent studies have implicated cysteine thiols present in various transcription factors, such as NF-kappaB, AP-1, and p53 as redox sensors in transcriptional regulation of many genes essential for maintaining cellular homeostasis. Some chemopreventive and cytoprotective agents have been found to target cysteine thiols present in key transcription factors or their regulators, thereby suppressing aberrant over-activation of carcinogenic signal transduction or restoring/normalizing or even potentiating cellular defense signaling. The focus of this review is the oxidation or covalent modification of thiol groups present in key representative redox-sensitive transcription factors and their regulating molecules as a unique strategy for molecular target-based chemoprevention and cytoprotection.
Insights
Chemoprevention strategies target cysteine thiols in transcription factors like NF-kappaB to inhibit cancer. Modifying these redox sensors offers a molecular approach for cancer prevention and cell protection.
Area of Science:
- Molecular Biology
- Biochemistry
- Cancer Research
Background:
- Chemoprevention aims to inhibit or reverse carcinogenesis using non-toxic chemicals.
- Carcinogenesis involves complex signal transduction pathways.
- Transcription factors containing cysteine thiols act as redox sensors regulating cellular homeostasis.
Purpose of the Study:
- To review the role of cysteine thiols in transcription factors as targets for chemoprevention.
- To explore the modification of these thiol groups as a molecular strategy for cancer prevention and cytoprotection.
Main Methods:
- Review of recent studies on chemopreventive agents and their molecular targets.
- Focus on the oxidation and covalent modification of cysteine thiols in transcription factors.
- Analysis of signaling molecules involved in carcinogenesis and cellular defense.
Main Results:
- Cysteine thiols in transcription factors (e.g., NF-kappaB, AP-1, p53) are crucial redox sensors.
- Chemopreventive agents can target these cysteine thiols to modulate carcinogenic signaling.
- Modification of thiols can suppress aberrant signaling or enhance cellular defense mechanisms.
Conclusions:
- Targeting cysteine thiols in redox-sensitive transcription factors is a promising molecular strategy.
- This approach offers potential for effective chemoprevention and cytoprotection.
- Understanding these molecular mechanisms is key to developing novel cancer therapies.
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