Related Experiment Video

Updated: Jun 14, 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

Multifaceted regulation of sirtuin 2 (Sirt2) deacetylase activity

Maheeshi Yapa Abeywardana1, Samuel D Whedon1, Kwangwoon Lee1

  • 1Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA.

The Journal of Biological Chemistry
|August 30, 2024
PubMed

Insights

Sirtuin 2 (Sirt2) activity is regulated by its N and C termini. N-terminal phosphorylation enhances protein deacetylation, while VRK1 stimulates nucleosome deacetylation by Sirt2.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Epigenetics

Background:

  • Sirtuin 2 (Sirt2) is an NAD-dependent lysine deacylase involved in cell cycle and gene expression.
  • Sirt2 deacetylates both histone and nonhistone proteins.
  • Sirt2's N and C termini are subject to alternative splicing and posttranslational modifications like phosphorylation.

Purpose of the Study:

  • To investigate the role of Sirt2's N and C termini in regulating deacetylation of nuclear substrates.
  • To characterize the impact of N-terminal phosphorylation on Sirt2 activity.
  • To explore the interaction between VRK1 and Sirt2 in nucleosome deacetylation.

Main Methods:

  • Protein semisynthesis was employed to study Sirt2.
  • Investigated the effects of N-terminal phosphorylation at Ser23/Ser25.
  • Assessed the influence of VRK1 on Sirt2-mediated nucleosome deacetylation.

Main Results:

  • The C terminus of Sirt2 autoinhibits its deacetylation activity.
  • The N terminus enhances deacetylation of proteins and peptides, but not nucleosomes.
  • N-terminal phosphorylation further boosts protein/peptide deacetylation without affecting nucleosome deacetylation.
  • VRK1 stimulates Sirt2-mediated nucleosome deacetylation, potentially via electrostatic interactions.

Conclusions:

  • Sirt2 activity is modulated by its flexible termini and phosphorylation.
  • N-terminal modifications primarily affect protein/peptide deacetylation.
  • VRK1 plays a role in regulating Sirt2's interaction with chromatin.
  • These findings reveal diverse mechanisms controlling Sirt2's biological functions.
Keywords:
enzymeshistonesnucleosomesphosphorylationprotein semisynthesis,

More Related Videos

Assays for Validating Histone Acetyltransferase Inhibitors09:11

Assays for Validating Histone Acetyltransferase Inhibitors

Published on: August 6, 2020

6.5K
Simultaneous Affinity Enrichment of Two Post-Translational Modifications for Quantification and Site Localization12:11

Simultaneous Affinity Enrichment of Two Post-Translational Modifications for Quantification and Site Localization

Published on: February 27, 2020

6.8K

Related Concept Videos

Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
6.8K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K
Spreading of Chromatin Modifications02:25

Spreading of Chromatin Modifications

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...
8.2K
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
7.2K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

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...
3.4K