Related Experiment Video

Updated: Mar 1, 2026

Assaying Proteasomal Degradation in a Cell-free System in Plants
07:43

Assaying Proteasomal Degradation in a Cell-free System in Plants

Published on: March 26, 2014

15.1K

Activation of the FA pathway mediated by phosphorylation and ubiquitination

Masamichi Ishiai1, Koichi Sato2, Junya Tomida1

  • 1Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Kyoto University, Kyoto, Japan.

Mutation Research
|May 30, 2017
PubMed

Insights

Fanconi anemia (FA) is a genetic disorder affecting genome integrity. This review details how the FA pathway, crucial for DNA repair, is activated by protein modifications in response to DNA damage.

Area of Science:

  • Genetics
  • Molecular Biology
  • Biochemistry

Background:

  • Fanconi anemia (FA) is a hereditary disease impacting genome stability.
  • It is characterized by organ malformations, bone marrow failure, and cancer susceptibility.
  • The FA pathway, involving at least 21 proteins, repairs endogenous DNA damage, particularly interstrand crosslinks (ICLs).

Purpose of the Study:

  • To review the activation mechanisms of the FA pathway.
  • To summarize current knowledge on how protein modifications regulate FA pathway activation.

Main Methods:

  • Literature review of studies on Fanconi anemia and DNA repair pathways.
  • Focus on protein modifications and their role in FA pathway signaling.

Main Results:

  • The FA pathway is activated by DNA interstrand crosslinks (ICLs).
  • A key event in FA pathway activation is the mono-ubiquitination of the FANCD2-FANCI complex.
  • Recent findings highlight complex regulatory details in FA pathway activation.

Conclusions:

  • Protein modifications play a critical role in regulating the Fanconi anemia pathway.
  • Understanding these modifications is key to comprehending FA pathogenesis and potential therapeutic strategies.
Keywords:
DNA repairFanconi anemiaInterstrand crosslinkMono-ubiquitinationPhosphorylation

More Related Videos

Oligopeptide Competition Assay for Phosphorylation Site Determination09:16

Oligopeptide Competition Assay for Phosphorylation Site Determination

Published on: May 18, 2017

8.9K
Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates09:47

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates

Published on: May 10, 2022

3.2K

Related Concept Videos

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...
9.1K
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....
9.8K
The Proteasome01:13

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
1.9K
The Proteasome02:18

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
10.4K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

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...
8.8K
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...
5.9K