Related Experiment Video

Updated: May 16, 2026

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

The histone deacetylase SIRT2 stabilizes Myc oncoproteins

P Y Liu1, N Xu, A Malyukova

  • 1Children's Cancer Institute Australia for Medical Research, Randwick, Sydney, NSW 2031, Australia.

Cell Death and Differentiation
|November 24, 2012
PubMed

Insights

Scientists discovered that SIRT2 deacetylase stabilizes Myc oncoproteins, promoting cancer cell growth. Inhibiting SIRT2 reactivates NEDD4, which degrades Myc, offering a new therapeutic strategy for Myc-driven cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Myc oncoproteins are frequently upregulated in various human cancers.
  • Myc stabilization by Aurora A and degradation via the ubiquitin-proteasome pathway are critical for its oncogenic function.
  • Histone deacetylases (HDACs) are increasingly recognized as potential cancer therapeutic targets.

Purpose of the Study:

  • To investigate the role of the class III histone deacetylase, SIRT2, in the regulation of Myc oncoproteins in cancer.
  • To elucidate the molecular mechanisms by which SIRT2 influences Myc stability and cancer cell proliferation.
  • To evaluate the therapeutic potential of SIRT2 inhibitors in Myc-driven malignancies.

Main Methods:

  • Affymetrix gene array analysis to identify genes repressed by SIRT2.
  • Chromatin immunoprecipitation (ChIP) assays to assess SIRT2 binding to the NEDD4 gene promoter.
  • Western blotting to evaluate protein levels of Myc, NEDD4, and Aurora A.
  • Cell proliferation assays to assess the impact of SIRT2 modulation on cancer cells.

Main Results:

  • SIRT2 was upregulated by N-Myc in neuroblastoma and c-Myc in pancreatic cancer cells, enhancing Myc protein stability and promoting proliferation.
  • SIRT2 directly repressed NEDD4 gene expression by binding to its promoter and deacetylating histone H4 lysine 16.
  • NEDD4 directly targeted Myc oncoproteins for ubiquitination and degradation.
  • Small-molecule SIRT2 inhibitors reactivated NEDD4, reduced Myc protein levels, and suppressed cancer cell proliferation.
  • SIRT2 modulated Aurora A expression, with inhibitors decreasing its levels.

Conclusions:

  • A novel pathway involving SIRT2, NEDD4, and Myc oncoproteins in cancer development was identified.
  • SIRT2 enhances Myc oncoprotein stability and promotes cancer cell proliferation.
  • SIRT2 inhibitors represent a promising therapeutic strategy for Myc-induced malignancies by disrupting this regulatory pathway.

More Related Videos

Comparative Strategies for Ubiquitination Detection in Mammalian Cell Lysates Using SMAD2/SMURF2 as a Model09:00

Comparative Strategies for Ubiquitination Detection in Mammalian Cell Lysates Using SMAD2/SMURF2 as a Model

Published on: April 17, 2026

Assays for Validating Histone Acetyltransferase Inhibitors09:11

Assays for Validating Histone Acetyltransferase Inhibitors

Published on: August 6, 2020

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Histone Modification02:32

Histone Modification

The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Histone Modification02:32

Histone Modification

The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
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 is an enzyme that can...
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic cells are...
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.