Related Experiment Video

Updated: May 4, 2026

An In Vitro Model for Studying Cellular Transformation by Kaposi Sarcoma Herpesvirus
09:53

An In Vitro Model for Studying Cellular Transformation by Kaposi Sarcoma Herpesvirus

Published on: August 25, 2017

7.9K

Viral cyclin promotes KSHV-induced cellular transformation and tumorigenesis by overriding contact inhibition

Tiffany Jones1, Suzane Ramos da Silva2, Roble Bedolla3

  • 1Department of Molecular Medicine; University of Texas Health Science Center at San Antonio; San Antonio, TX USA; Department of Molecular Microbiology and Immunology; Keck School of Medicine; University of Southern California; Los Angeles, CA USA.

Cell Cycle (Georgetown, Tex.)
|January 15, 2014
PubMed

Insights

Kaposi sarcoma-associated herpesvirus (KSHV) vCyclin promotes cancer by overriding cell cycle arrest when cells are crowded. Deleting vCyclin reduces tumor formation and growth in mice.

Area of Science:

  • Oncology
  • Virology
  • Cell Biology

Background:

  • Kaposi sarcoma-associated herpesvirus (KSHV) is a tumor virus with oncogenic potential.
  • The specific roles of KSHV-encoded proto-oncogenes in tumorigenesis remain largely undefined.

Purpose of the Study:

  • To investigate the function of the KSHV latent gene vCyclin (ORF72), a homolog of cellular Cyclin D2, in KSHV-induced oncogenesis.
  • To elucidate the mechanisms by which vCyclin contributes to cellular transformation and tumor development.

Main Methods:

  • Utilized a KSHV-induced cellular transformation and tumorigenesis model combined with a reverse genetic system.
  • Generated and analyzed vCyclin deletion mutants.
  • Assessed cell proliferation, cell cycle progression, soft agar colony formation, and tumor development in nude mice.
  • Investigated the phosphorylation and localization of p27/Kip1 and employed shRNA knockdown of p27.

Main Results:

  • vCyclin deletion did not impact proliferation at low cell density but caused G1 arrest at high density.
  • vCyclin mutant cells exhibited reduced soft agar colony formation.
  • Mice inoculated with vCyclin mutant KSHV showed decreased tumor incidence, longer latency, and increased survival.
  • Wild-type KSHV, but not mutant virus, induced p27/Kip1 phosphorylation and cytoplasmic relocalization; p27 knockdown rescued the mutant phenotype.

Conclusions:

  • vCyclin is crucial for enhancing cellular transformation and tumorigenesis.
  • vCyclin promotes cell cycle progression and proliferation, particularly under contact-inhibited conditions.
  • The mechanism involves the regulation of p27/Kip1 activity and localization.
Keywords:
KSHVKaposi sarcomacell cycle progressioncell proliferationcellular transformationcontact inhibitionp27/Kip1tumorigenesisvCyclin/ORF72

More Related Videos

Establishment and Quantification of De Novo Lytic Infection by Cell-free Kaposi's Sarcoma-Associated Herpesvirus07:10

Establishment and Quantification of De Novo Lytic Infection by Cell-free Kaposi's Sarcoma-Associated Herpesvirus

Published on: August 15, 2025

926
Identifying Dysregulated Genes Induced by Kaposi's Sarcoma-associated Herpesvirus KSHV07:02

Identifying Dysregulated Genes Induced by Kaposi's Sarcoma-associated Herpesvirus KSHV

Published on: September 14, 2010

12.1K

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.8K
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

4.3K
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...
5.2K
Mechanisms of Retrovirus-induced Cancers01:51

Mechanisms of Retrovirus-induced Cancers

2.8K
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
2.5K
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
5.3K