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.

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.

Related Concept Videos

Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
Chromatin Structure Regulates pre-mRNA Processing02:41

Chromatin Structure Regulates pre-mRNA Processing

In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
Transcription Attenuation in Prokaryotes02:42

Transcription Attenuation in Prokaryotes

Transcriptional attenuation occurs when RNA transcription is prematurely terminated due to the formation of a terminator mRNA hairpin structure.  Bacteria use these hairpins to regulate the transcription process and control the synthesis of several amino acids including histidine, lysine, threonine, and phenylalanine. Transcription attenuation takes place in the non-coding regions of mRNA.
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...