Related Experiment Video
Updated: Aug 13, 2025
09:20
In situ Subcellular Fractionation of Adherent and Non-adherent Mammalian Cells
Published on: July 23, 2010
15.8K
Master mitotic kinases regulate viral genome delivery during papillomavirus cell entry
Matteo Rizzato1, Fuxiang Mao1, Florian Chardon1
1Institute of Cellular Virology, Westphalian Wilhelms-University of Münster, Münster, Germany.
Nature Communications
|January 22, 2023
Summary
Mitotic kinases CDK1 and PLK1 phosphorylate human papillomavirus (HPV) minor capsid protein L2, enabling viral DNA delivery to mitotic chromosomes. This phosphorylation regulates pathogen import into the nucleus during cell division.
Area of Science:
- Cell Biology
- Virology
- Molecular Biology
Background:
- Mitosis involves significant cellular rearrangements, including nuclear envelope breakdown.
- Nuclear entry of human papillomavirus (HPV) genomes utilizes mitosis, with the L2 protein tethering viral DNA to mitotic chromosomes.
- The precise mechanisms and regulatory factors governing HPV genome delivery to chromosomes during mitosis remain largely unknown.
Purpose of the Study:
- To elucidate the molecular mechanisms of HPV genome tethering to mitotic chromosomes.
- To identify cellular proteins and regulatory processes involved in HPV nuclear import during mitosis.
- To investigate the role of L2 protein modifications during mitosis.
Main Methods:
- Phosphorylation site analysis of HPV minor capsid protein L2.
- In vitro kinase assays using CDK1 and PLK1.
- Chromatin binding assays to assess L2-chromosome interactions.
Main Results:
- Identified specific phosphorylation sites on L2 crucial for mitosis.
- Demonstrated sequential phosphorylation of L2's chromosome binding region (CBR) by CDK1 and PLK1.
- Showed that L2 phosphorylation regulates the timely delivery of HPV viral DNA (vDNA) to mitotic chromatin.
Conclusions:
- Mitotic kinases CDK1 and PLK1 play a critical role in regulating HPV L2 phosphorylation.
- L2 phosphorylation is essential for the efficient tethering of viral DNA to mitotic chromosomes.
- This study provides key insights into the molecular mechanisms of nuclear import of viral DNA during mitosis.
Related Concept Videos
02:15M-Cdk Drives Transition Into Mitosis
5.7K
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
5.7K
02:34Inhibition of Cdk Activity
4.9K
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...
4.9K
02:38Mitogens and the Cell Cycle
6.6K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.6K
01:51Mechanisms of Retrovirus-induced Cancers
5.2K
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
02:39Positive Regulator Molecules
5.6K
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.
5.6K
01:23Negative Regulator Molecules
35.5K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.5K