Steroid receptor coactivator-1 coactivates activating protein-1-mediated transactivations through interaction with

S K Lee1, H J Kim, S Y Na

  • 1College of Pharmacy, Chonnam National University, Kwangju 500-757, Korea.

Insights

Steroid receptor coactivator-1 (SRC-1) binds transcription factor AP-1. SRC-1 and p300 cooperate to regulate AP-1 activity and gene repression involving nuclear receptors.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Protein-Protein Interactions

Background:

  • Steroid receptor coactivator-1 (SRC-1) is a key transcriptional coactivator.
  • The transcription factor AP-1, composed of c-Jun and c-Fos, regulates gene expression.
  • Cross-talk between AP-1 and nuclear receptors influences cellular responses.

Purpose of the Study:

  • To investigate the interaction between SRC-1 and AP-1 subunits.
  • To determine the functional consequences of SRC-1 binding to AP-1.
  • To elucidate the role of coactivators in mediating cross-talk between AP-1 and nuclear receptors.

Main Methods:

  • Yeast two-hybrid assays to detect protein-protein interactions.
  • Glutathione S-transferase (GST) pull-down assays to confirm binding.
  • Mammalian cell transfections to assess transcriptional activity.

Main Results:

  • SRC-1 directly binds to c-Jun and c-Fos subunits of AP-1.
  • The binding site for c-Jun and c-Fos on SRC-1 is located in its C-terminal region (amino acids 1101-1441).
  • SRC-1 potentiates AP-1-mediated transactivation and derepresses mutual inhibition between AP-1 and nuclear receptors.
  • Coexpression of p300 enhances SRC-1-mediated potentiation of AP-1 transactivation.

Conclusions:

  • SRC-1 interacts with AP-1, modulating its transcriptional activity.
  • Cooperation between SRC-1 and p300 is crucial for regulating AP-1-dependent transcription.
  • These coactivators mediate transrepression between AP-1 and nuclear receptors in vivo.

Related Concept Videos

RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
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 Activators02:42

Eukaryotic Transcription Activators

Transcription activators are proteins that promote the transcription of genes from DNA to RNA. In most cases, these proteins contain two separate domains ‒ a domain that binds to DNA and a domain for activating transcription; however, in some cases, a single domain is responsible for both binding and activation of transcription, as seen in the glucocorticoid receptor and MyoD.
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These domains are...
RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
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...