Related Experiment Video

Updated: Jan 2, 2026

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
06:38

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis

Published on: September 12, 2019

9.4K

A fail-safe system to prevent oncogenesis by senescence is targeted by SV40 small T antigen

Kiyotaka Oshikawa1, Masaki Matsumoto2, Manabu Kodama1

  • 1Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.

Oncogene
|December 11, 2019
PubMed

Insights

Simian virus 40 small T antigen (ST) promotes oncogenesis by inhibiting a cellular defense mechanism. ST interferes with the HP1BP3-BTG2 pathway, preventing oncogene-induced senescence and promoting tumor growth.

Area of Science:

  • Molecular Biology
  • Virology
  • Oncology

Background:

  • Large T antigen (LT) of simian virus 40 (SV40) is known to promote oncogenesis by inactivating tumor suppressors p53 and pRb.
  • SV40 small T antigen (ST) has been considered non-essential for SV40-mediated oncogenesis.

Purpose of the Study:

  • To investigate the role of SV40 ST in oncogenesis, particularly its interaction with oncogene-ras-induced cellular responses.
  • To elucidate the molecular mechanisms by which ST influences oncogenesis and cellular senescence.

Main Methods:

  • Utilized human cells expressing oncogenic Ras.
  • Analyzed the effects of SV40 LT and ST on cell growth, senescence, and the senescence-associated secretory phenotype (SASP).
  • Investigated the interaction of ST with HP1BP3 and its impact on microRNA biogenesis and BTG2 expression.

Main Results:

  • LT induced both oncogenic growth and senescence in Ras-expressing cells.
  • ST antagonized LT-induced senescence, attenuating the SASP and promoting efficient oncogenesis.
  • ST inhibited HP1BP3, a regulator of microRNA biogenesis, leading to BTG2 upregulation.
  • The HP1BP3-BTG2 axis was identified as a critical pathway for preventing SASP and oncogene-induced senescence (OIS).

Conclusions:

  • SV40 ST actively promotes oncogenesis by hijacking the HP1BP3-BTG2 cellular defense system.
  • ST's inhibition of HP1BP3 and subsequent BTG2 upregulation are crucial for overcoming OIS and facilitating tumor development.

More Related Videos

Tailoring In Vivo Cytotoxicity Assays to Study Immunodominance in Tumor-specific CD8+ T Cell Responses10:13

Tailoring In Vivo Cytotoxicity Assays to Study Immunodominance in Tumor-specific CD8+ T Cell Responses

Published on: May 6, 2019

9.4K
Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer08:34

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer

Published on: April 13, 2015

10.7K

Related Concept Videos

Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
4.2K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.3K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
5.8K
Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
6.1K
Mechanisms of Retrovirus-induced Cancers01:51

Mechanisms of Retrovirus-induced Cancers

Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
6.8K