A peptide-based synthetic transcription factor selectively down-regulates the proto-oncogene CFOS in tumour cells and

Madhumita Chakraborty1, Siddhartha Roy1

  • 1Department of Biophysics, Bose Institute, P-1/12 CIT Scheme VII M, Kolkata 700054, India. sidroykolkata@gmail.com.

Chemical Communications (Cambridge, England)
|December 10, 2016
PubMed

Insights

Scientists created a synthetic transcription factor using peptides. This molecule precisely controls gene activity in tumor cells, stopping their growth.

Area of Science:

  • Chemical Biology
  • Molecular Biology
  • Synthetic Biology

Background:

  • Precise control over gene expression is crucial in chemical biology.
  • Developing tools for targeted gene regulation remains a significant challenge.

Purpose of the Study:

  • To engineer a novel peptide-based synthetic transcription factor.
  • To achieve high-affinity DNA binding with single base-pair specificity.
  • To demonstrate selective gene regulation and inhibition of cancer cell proliferation.

Main Methods:

  • Design and synthesis of a peptide-based transcription factor.
  • Assay of DNA binding affinity and specificity.
  • Delivery of the synthetic transcription factor into tumor cells.
  • Analysis of targeted gene expression and cell proliferation.

Main Results:

  • The synthetic transcription factor exhibited high-affinity binding to target DNA sequences.
  • It demonstrated precise discrimination at the single base-pair level.
  • Intracellular delivery led to selective regulation of targeted genes.
  • Significant inhibition of tumor cell proliferation was observed.

Conclusions:

  • A novel peptide-based synthetic transcription factor was successfully developed.
  • This tool offers precise control over gene expression with high specificity.
  • The findings highlight potential therapeutic applications in cancer treatment.

Related Concept Videos

Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
8.0K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.4K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.9K
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
11.2K
Transcription Factors02:16

Transcription Factors

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
83.4K
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
8.8K