Related Experiment Video

Updated: Oct 29, 2025

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

9.7K

p53 deficiency induces MTHFD2 transcription to promote cell proliferation and restrain DNA damage

Gen Li1,2, Jun Wu1,2, Le Li1,2

  • 1School of Life Sciences, Tsinghua University, Beijing 100084, China.

Proceedings of the National Academy of Sciences of the United States of America
|July 10, 2021
PubMed

Insights

The study reveals methylenetetrahydrofolate dehydrogenase (MTHFD2) promotes cancer growth by aiding DNA repair in p53-deficient cells. Depleting MTHFD2 may offer a new treatment strategy for these tumors.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Cancer cells exhibit metabolic reprogramming to meet high biosynthetic demands.
  • The role of metabolic remodeling in cancer cell survival under genomic instability is not well understood.

Purpose of the Study:

  • To investigate the role of methylenetetrahydrofolate dehydrogenase (MTHFD2) in p53-deficient cancer cells.
  • To explore MTHFD2's function in DNA damage repair and its implications for tumor growth and treatment.

Main Methods:

  • Analysis of MTHFD2 transcriptional regulation by p53.
  • Assessment of folate metabolism and de novo purine synthesis.
  • Investigation of MTHFD2's interaction with PARP3 in DNA repair.
  • Evaluation of MTHFD2 depletion effects on cell proliferation and chemosensitivity.

Main Results:

  • MTHFD2 is transcriptionally suppressed by p53; its upregulation upon p53 inactivation increases folate metabolism, purine synthesis, and tumor growth.
  • MTHFD2 promotes nonhomologous end joining DNA repair by complexing with PARP3.
  • An inactive MTHFD2 mutant disrupts this DNA repair function.
  • MTHFD2 depletion inhibits p53-deficient cell proliferation and enhances sensitivity to chemotherapy.

Conclusions:

  • MTHFD2 plays a critical role in supporting p53-deficient tumor growth and survival through enhanced metabolism and DNA repair.
  • Targeting MTHFD2 represents a potential therapeutic strategy for p53-deficient cancers.
Keywords:
MTHFD2NHEJcell proliferationfolate metabolismp53

More Related Videos

Purification of Ubiquitinated p53 Proteins from Mammalian Cells10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

2.4K
Establishment of Proliferative Tetraploid Cells from Nontransformed Human Fibroblasts10:04

Establishment of Proliferative Tetraploid Cells from Nontransformed Human Fibroblasts

Published on: January 8, 2017

7.4K

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...
4.8K
DNA Damage can Stall the Cell Cycle02:37

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.6K
DNA Damage Can Stall the Cell Cycle02:37

DNA Damage Can Stall the Cell Cycle

2.8K
Negative Regulator Molecules01:23

Negative Regulator Molecules

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.
36.7K
Molecular Factors Affecting Cell Division01:27

Molecular Factors Affecting Cell Division

Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
3.5K
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...
5.1K