Related Experiment Video

Updated: Jan 25, 2026

Studying the Protein Quality Control System of D. discoideum Using Temperature-controlled Live Cell Imaging
06:09

Studying the Protein Quality Control System of D. discoideum Using Temperature-controlled Live Cell Imaging

Published on: December 2, 2016

7.4K

L3MBTL1 regulates ALS/FTD-associated proteotoxicity and quality control

Jiayin Lu1,2, Goran Periz1,2, Yu-Ning Lu1,2

  • 1Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.

Nature Neuroscience
|May 8, 2019
PubMed

Insights

Lethal(3)malignant brain tumor-like protein 1 (L3MBTL1) regulates protein quality control, protecting against neurodegenerative disease. Its loss shields neurons from toxic protein buildup, offering therapeutic potential for conditions like ALS and FTD.

Area of Science:

  • Neurobiology
  • Molecular Biology
  • Genetics

Background:

  • Misfolded protein accumulation and impaired protein quality control are hallmarks of neurodegenerative diseases like ALS and FTD.
  • Identifying key regulators of protein quality control is crucial for understanding disease mechanisms.

Purpose of the Study:

  • To identify novel regulators of protein quality control involved in neurodegeneration.
  • To elucidate the role of Lethal(3)malignant brain tumor-like protein 1 (L3MBTL1) in protein quality control and neuroprotection.

Main Methods:

  • Proteotoxicity assays using mutant proteins (SOD1, C9orf72 repeats).
  • Analysis of p53-dependent protein degradation pathways.
  • Western blotting and immunohistochemistry in cell and animal models.
  • Comparative analysis across species (C. elegans to mammals).

Main Results:

  • L3MBTL1 was identified as a key regulator of protein quality control.
  • Loss of L3MBTL1 conferred protection against proteotoxicity from mutant SOD1 and C9orf72 proteins.
  • L3MBTL1 regulates p53-dependent degradation of misfolded proteins.
  • SET domain-containing protein 8, an L3MBTL1-associated protein, also impacts protein clearance.
  • L3MBTL1 and SETDB1 are upregulated in ALS/FTD models and patients.
  • L3MBTL1's function in protein quality control is evolutionarily conserved.

Conclusions:

  • A novel protein quality control pathway involving L3MBTL1 and SETDB1 is revealed.
  • This pathway is critical for cellular stress response and implicated in proteotoxicity-driven neurodegenerative diseases.
  • Targeting this pathway may offer therapeutic strategies for ALS and FTD.

More Related Videos

Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation08:00

Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation

Published on: October 4, 2024

1.1K
DNA Microarrays: Sample Quality Control, Array Hybridization and Scanning09:27

DNA Microarrays: Sample Quality Control, Array Hybridization and Scanning

Published on: March 15, 2011

38.6K

Related Concept Videos

Quality Control01:05

Quality Control

Quality control is one of the three cyclical quality assurance activities that help keep a system under statistical control. Typical quality control activities include creating quality control charts, conducting proficiency testing, and documenting and archiving results.
Quality control helps track data, visualize trends, and identify variations, making it easier to detect deviations that may affect the accuracy of an analysis. One way to do this is by generating a quality control chart, which...
1.4K
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...
8.8K
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.7K
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
33.5K
GTPases and their Regulation02:14

GTPases and their Regulation

Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒  small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins,...
9.8K
Quality of Water01:19

Quality of Water

In concrete preparation, the quality of water is paramount as it affects the strength and durability of the concrete. Potable water is usually preferred; however, it must not have excessive sodium or potassium to prevent compromising the concrete's integrity. Water quality is typically evaluated based on impurities such as dissolved solids, chlorides, and sulfates, and its pH value is ideally between 6 and 8. Even slightly acidic natural water may be acceptable unless it contains harmful...
516