Related Experiment Video

Updated: Aug 1, 2026

Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins
11:34

Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins

Published on: August 9, 2019

Binding of p300/CBP co-activators by polyoma large T antigen

S Cho1, Y Tian, T L Benjamin

  • 1Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.

The Journal of Biological Chemistry
|July 5, 2001
PubMed

Insights

Polyomavirus large T antigen binds to CBP, a protein that regulates gene activity. This interaction is crucial for tumor virus replication and spread in hosts, impacting cell transformation and tumor formation.

Area of Science:

  • Virology
  • Molecular Biology
  • Oncology

Background:

  • Small DNA tumor viruses like SV40 and Polyomavirus utilize host cell proteins for replication and transcription.
  • Viral T antigens interacting with host proteins can lead to cell transformation and tumor induction.
  • SV40 large T antigen interacts with p53, pRb family members, and CBP/p300, while Py large T was known to interact with pRb and p300.

Purpose of the Study:

  • To investigate the interaction between Polyomavirus (Py) large T antigen and CBP (CREB-binding protein).
  • To determine the role of Py large T antigen's interaction with CBP/p300 in gene transactivation.
  • To assess the significance of Py large T:CBP interaction in viral oncogenesis and pathogenesis.

Main Methods:

  • In vivo and in vitro binding assays to confirm Py large T antigen interaction with CBP.
  • Co-transfection assays to evaluate the effect of Py large T on CREB- and NF-kappa B-mediated transactivation.
  • Site-directed mutagenesis of Py large T antigen to identify critical regions for co-activator binding and functional analysis.

Main Results:

  • Py large T antigen binds to CBP both in vivo and in vitro.
  • Py large T inhibits CBP/p300 co-activation of CREB-mediated transactivation but not NF-kappa B-mediated transactivation.
  • Mutations in a conserved region of Py large T disrupt CBP/p300 binding and inhibit CREB transactivation, yet still allow for fibroblast transformation but impair tumor induction in mice.

Conclusions:

  • Py large T antigen interacts with CBP, expanding the known host protein interactions for this viral protein.
  • The interaction between Py large T and CBP/p300 is critical for regulating CREB-mediated gene expression.
  • While CBP/p300 binding is essential for Py large T-induced tumor formation in vivo, it is not strictly required for initial cell transformation, suggesting a role in viral spread and pathogenesis.

More Related Videos

Measurement of BK-polyomavirus Non-Coding Control Region Driven Transcriptional Activity Via Flow Cytometry11:54

Measurement of BK-polyomavirus Non-Coding Control Region Driven Transcriptional Activity Via Flow Cytometry

Published on: July 13, 2019

Assays for Validating Histone Acetyltransferase Inhibitors09:11

Assays for Validating Histone Acetyltransferase Inhibitors

Published on: August 6, 2020

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...
Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...
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...
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...
General Transcription Factors01:30

General 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...