Steroid receptor coactivator-1 and its family members differentially regulate transactivation by the tumor suppressor

S K Lee1, H J Kim, J W Kim

  • 1Department of Biology, Chonnam National University, Kwangju, Korea.

Insights

The tumor suppressor protein p53 interacts with steroid receptor coactivator-1 (SRC-1) family members. These interactions differentially modulate p53-mediated gene activation, impacting cell cycle regulation.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • The tumor suppressor protein p53 is a transcription factor regulating cell cycle.
  • Steroid receptor coactivator-1 (SRC-1) and its family members are coactivators for nuclear receptors.

Purpose of the Study:

  • To investigate the interaction between p53 and SRC-1 family members.
  • To determine how these interactions affect p53-mediated transactivation.

Main Methods:

  • Yeast and mammalian two-hybrid assays.
  • Glutathione S-transferase (GST) pull-down assays.
  • Cotransfection of HeLa cells with expression vectors.

Main Results:

  • p53 physically interacts with SRC-1, p/CIP, xSRC-3, and AIB1.
  • SRC-1 and p/CIP potentiated p53-mediated transactivation.
  • AIB1 and xSRC-3 repressed p53-mediated transactivation.
  • All SRC-1 members stimulated nuclear receptor and AP-1 transactivation.

Conclusions:

  • SRC-1 family members differentially modulate p53 transactivation in vivo.
  • These findings reveal a novel regulatory mechanism for p53 function.

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.
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...
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...
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.
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...