Transcriptional repression by the C-terminal domain of p53

E Shaulian1, I Haviv, Y Shaul

  • 1Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.

Oncogene
|February 16, 1995
PubMed

Insights

Monomeric p53 protein (p53) transactivates genes, but C-terminal fragments can be oncogenic. Truncated p53 retains some function, while C-terminal fragments inhibit p53

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Gene Regulation

Background:

  • Monomeric p53 protein (p53) exhibits transactivation capabilities for target genes in vivo.
  • C-terminal fragments of p53 have been identified as oncogenic.
  • Previous research established the roles of p53 in gene regulation and oncogenesis.

Purpose of the Study:

  • To investigate the functional consequences of C-terminal truncations of p53.
  • To assess the transactivation capacity of truncated p53 variants.
  • To determine the impact of C-terminal fragments on oncogene-mediated transformation and p53 activity.

Main Methods:

  • Generation of a series of C-terminal p53 truncations.
  • Assays to evaluate transactivation capacity of truncated p53.
  • Experiments to study the suppression of oncogene-mediated transformation by truncated p53.
  • Analysis of the inhibitory effects of C-terminal fragments on wild-type p53 and truncated p53 transactivation.

Main Results:

  • p53 truncated at amino acid 303 (p53wtdl303) retains partial transactivation and tumor suppressor functions, albeit less efficiently than full-length wild-type p53.
  • Oncogenic C-terminal fragments of p53 inhibit transactivation by both full-length wild-type p53 and p53wtdl303.
  • These C-terminal fragments also repress the transactivation domains of various viral and cellular transcriptional activators.

Conclusions:

  • The C-terminal domain of p53 may play a role in regulating its transactivation function.
  • C-terminal fragments of p53 can interfere with transcriptional activation, potentially through competition for a common basal transcription factor.
  • These findings suggest a novel mechanism of p53 regulation and potential therapeutic targets in cancer.

Related Concept Videos

Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
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...
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 DNA...
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...
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 daughter...
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...