Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

4.8K
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
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

3.8K
The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.8K
Histone Modification02:32

Histone Modification

3.5K
3.5K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

9.1K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
9.1K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

5.8K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.8K
Spreading of Chromatin Modifications02:25

Spreading of Chromatin Modifications

8.3K
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
8.3K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Nuclear functions regulated by the VRK1 kinase.

Nucleus (Austin, Tex.)·2024
Same author

VRK1 Regulates Sensitivity to Oxidative Stress by Altering Histone Epigenetic Modifications and the Nuclear Phosphoproteome in Tumor Cells.

International journal of molecular sciences·2024
Same author

Pathogenic effects of Leu200Pro and Arg387His VRK1 protein variants on phosphorylation targets and H4K16 acetylation in distal hereditary motor neuropathy.

Journal of molecular medicine (Berlin, Germany)·2024
Same author

The pattern of histone H3 epigenetic posttranslational modifications is regulated by the VRK1 chromatin kinase.

Epigenetics & chromatin·2023
Same author

Targeting Histone Epigenetic Modifications and DNA Damage Responses in Synthetic Lethality Strategies in Cancer?

Cancers·2022
Same author

Dysfunctional Homozygous VRK1-D263G Variant Impairs the Assembly of Cajal Bodies and DNA Damage Response in Hereditary Spastic Paraplegia.

Neurology. Genetics·2021

Related Experiment Video

Updated: Aug 7, 2025

Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates
14:32

Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates

Published on: February 27, 2016

8.3K

VRK1 Kinase Activity Modulating Histone H4K16 Acetylation Inhibited by SIRT2 and VRK-IN-1.

Eva Monte-Serrano1,2, Pedro A Lazo1,2

  • 1Molecular Mechanisms of Cancer Program, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad de Salamanca, E-37007 Salamanca, Spain.

International Journal of Molecular Sciences
|March 11, 2023
PubMed
Summary

The protein kinase VRK1 and deacetylase SIRT2 form a complex, inhibiting VRK1

Keywords:
DNA damage responseKAT5SIRT2Tip60VRK-IN-1VRK1acetylationhistone H4

More Related Videos

Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle
10:05

Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle

Published on: March 5, 2019

6.5K
Characterizing Histone Post-translational Modification Alterations in Yeast Neurodegenerative Proteinopathy Models
08:33

Characterizing Histone Post-translational Modification Alterations in Yeast Neurodegenerative Proteinopathy Models

Published on: March 24, 2019

7.6K

Related Experiment Videos

Last Updated: Aug 7, 2025

Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates
14:32

Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates

Published on: February 27, 2016

8.3K
Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle
10:05

Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle

Published on: March 5, 2019

6.5K
Characterizing Histone Post-translational Modification Alterations in Yeast Neurodegenerative Proteinopathy Models
08:33

Characterizing Histone Post-translational Modification Alterations in Yeast Neurodegenerative Proteinopathy Models

Published on: March 24, 2019

7.6K

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Biochemistry

Background:

  • Chromatin organization regulates DNA accessibility for cellular functions.
  • Histone H4 lysine 16 acetylation (H4K16ac) is a key epigenetic mark controlling chromatin accessibility.
  • H4K16ac levels are determined by the balance between histone acetyltransferases (e.g., Tip60/KAT5) and deacetylases (e.g., SIRT2).

Purpose of the Study:

  • To investigate the regulatory relationship between VRK1 and SIRT2 in controlling H4K16ac.
  • To elucidate the mechanism by which VRK1 and SIRT2 interact and affect H4K16ac.
  • To explore the therapeutic potential of targeting this interaction for DNA damage response.

Main Methods:

  • In vitro interaction assays (pull-down assays).
  • In vitro kinase assays.
  • Cellular studies including immunoprecipitation and immunofluorescence.
  • Inhibition studies using specific VRK1 and SIRT2 inhibitors.

Main Results:

  • VRK1 and SIRT2 form a stable protein complex.
  • SIRT2 directly inhibits VRK1 kinase activity through interaction with its N-terminal domain.
  • This interaction leads to decreased H4K16ac, similar to VRK1 inhibition or depletion.
  • SIRT2 inhibition in lung adenocarcinoma cells increases H4K16ac, while VRK1 inhibition decreases it.
  • VRK1 inhibition impairs DNA damage response.

Conclusions:

  • The interaction between VRK1 and SIRT2 is a critical regulatory mechanism for H4K16ac.
  • Targeting SIRT2 may enhance chromatin accessibility for DNA damage drugs, potentially cooperating with VRK1.
  • Understanding this interplay offers insights into epigenetic regulation and therapeutic strategies for cancer treatment.