Related Experiment Video

Updated: Dec 12, 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

8.5K

CSAG2 is a cancer-specific activator of SIRT1

Xu Yang1, Patrick Ryan Potts1

  • 1Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.

EMBO Reports
|August 8, 2020
PubMed

Insights

A newly discovered protein, CSAG2, directly activates SIRT1 (a deacetylase that inactivates the p53 tumor suppressor). This CSAG2-SIRT1 interaction promotes cancer cell growth and survival, offering new therapeutic targets.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Biology

Background:

  • SIRT1 is a key deacetylase regulating metabolism and signaling, including p53 tumor suppressor inactivation.
  • Mechanisms controlling SIRT1 activity in cancer remain largely unknown.

Purpose of the Study:

  • To identify novel regulators of SIRT1 activity in cancer.
  • To investigate the role of the previously undescribed CSAG2 protein in SIRT1 function and cancer.

Main Methods:

  • Biochemical assays to determine CSAG2 interaction with SIRT1.
  • Enzymatic activity assays measuring SIRT1 deacetylation of substrates, including p53.
  • In vivo tumorigenesis studies and in vitro cancer cell proliferation assays.

Main Results:

  • CSAG2 directly binds to and activates SIRT1 enzymatic activity.
  • CSAG2 re-expression in cancers enhances SIRT1-mediated p53 deacetylation and inhibition.
  • CSAG2 is essential for cancer cell proliferation and promotes tumor growth in vivo.
  • CSAG2 activates SIRT1 via direct binding to its catalytic domain, independent of substrate affinity changes.

Conclusions:

  • CSAG2 is a novel, direct activator of SIRT1, particularly relevant in cancer.
  • CSAG2-mediated SIRT1 activation provides a new mechanism for controlling p53 and promoting cancer cell survival.
  • Targeting the CSAG2-SIRT1 interaction presents a potential therapeutic strategy for cancer treatment.
Keywords:
NAD+-dependent deacetylaseapoptosiscancer-testis antigengenotoxic stressoncogene

More Related Videos

Cancer-Associated Fibroblasts from Mouse Mammary Tumors as Tools for Molecular and Computational Studies09:01

Cancer-Associated Fibroblasts from Mouse Mammary Tumors as Tools for Molecular and Computational Studies

Published on: July 3, 2025

702
Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures07:48

Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures

Published on: December 26, 2016

11.7K

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.5K
Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
5.9K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.2K
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...
5.4K
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
10.9K
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...
5.0K