Related Experiment Video

Updated: Oct 13, 2025

Application of AlDeSense to Stratify Ovarian Cancer Cells Based on Aldehyde Dehydrogenase 1A1 Activity
09:59

Application of AlDeSense to Stratify Ovarian Cancer Cells Based on Aldehyde Dehydrogenase 1A1 Activity

Published on: March 31, 2023

1.2K

AMBRA1 Negatively Regulates the Function of ALDH1B1, a Cancer Stem Cell Marker, by Controlling Its Ubiquitination

Seung-Heon Baek1,2, Yeun-Kyu Jang1,2

  • 1Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.

International Journal of Molecular Sciences
|November 13, 2021
PubMed

Insights

Activating molecule in Beclin-1-regulated autophagy (AMBRA1) negatively regulates aldehyde dehydrogenase 1 family member B1 (ALDH1B1) through noncanonical ubiquitination. This interaction impacts cancer stem cell marker expression and carcinogenesis pathways.

Area of Science:

  • Cellular biology
  • Molecular oncology
  • Ubiquitination pathways

Background:

  • Activating molecule in Beclin-1-regulated autophagy (AMBRA1) is a tumor suppressor and ubiquitin system component.
  • Aldehyde dehydrogenase 1 family member B1 (ALDH1B1) is a cancer stem cell marker crucial for carcinogenesis via the β-catenin pathway.
  • The ubiquitination-mediated regulation of ALDH1B1 remains largely uncharacterized.

Purpose of the Study:

  • To investigate the interaction and regulatory relationship between AMBRA1 and ALDH1B1.
  • To elucidate the mechanism by which AMBRA1 influences ALDH1B1 expression and function.
  • To determine the role of ubiquitination in ALDH1B1 regulation.

Main Methods:

  • Proteome analysis to suggest potential interactions.
  • Expression analysis of ALDH1B1-regulated genes.
  • Ubiquitination assays, including K27- and K33-linked ubiquitination mapping.
  • Site-directed mutagenesis to identify ubiquitination sites.
  • Analysis of ALDH1B1 self-association using ubiquitination-defective mutants.

Main Results:

  • AMBRA1 negatively regulates ALDH1B1 expression and its downstream targets, including PTEN and CTNNB1 (β-catenin).
  • AMBRA1 cooperates with E3 ligases like TRAF6 to mediate K27- and K33-linked ubiquitination of ALDH1B1.
  • Specific lysine residues (K506, K511, K515 for K27; K506 for K33) were identified as critical ubiquitination sites.
  • ALDH1B1 ubiquitination inversely correlates with its self-association ability.

Conclusions:

  • AMBRA1 acts as a negative regulator of ALDH1B1.
  • AMBRA1-mediated noncanonical ubiquitination is a key mechanism controlling ALDH1B1 stability and function.
  • These findings reveal a novel regulatory axis impacting cancer stem cell pathways.
Keywords:
E3 ubiquitin ligasealdehyde dehydrogenase 1B1colorectal cancer stem cellnoncanonical ubiquitinationsubstrate receptor

More Related Videos

Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog08:37

Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog

Published on: November 5, 2014

10.1K
In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones11:36

In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones

Published on: July 25, 2019

11.0K

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...
4.7K
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
6.0K
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
6.0K
Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
5.1K
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...
7.9K
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.
36.5K