Related Experiment Video
Updated: May 24, 2026
11:36
In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
Published on: July 25, 2019
Hedgehog/Gli control by ubiquitination/acetylation interplay.
Alberto Gulino1, Lucia Di Marcotullio, Gianluca Canettieri
1Department of Molecular Medicine, Sapienza University, Rome, Italy.
Vitamins and Hormones
|March 7, 2012
Summary
Hedgehog signaling, crucial for development, is tightly regulated by Gli ubiquitination. This process, involving E3 ligases, controls Gli activity and impacts tumorigenesis, offering potential therapeutic targets.
Area of Science:
- Molecular Biology
- Developmental Biology
- Cancer Biology
Background:
- Hedgehog (Hh) signaling is a critical pathway regulating embryonic development.
- Aberrant Hh pathway activation is implicated in various human cancers, promoting tumorigenesis.
- The Gli family of transcription factors are the primary mediators of Hh signaling.
Purpose of the Study:
- To elucidate the role of ubiquitination in regulating Gli transcription factors.
- To identify the E3 ligases involved in Gli ubiquitination and their regulatory mechanisms.
- To explore the therapeutic potential of targeting Gli ubiquitination in Hh-driven cancers.
Main Methods:
- Investigated posttranslational modifications of Gli proteins, focusing on ubiquitination.
- Identified and characterized E3 ligases (RING/Cullin and HECT families) that target Gli for degradation.
- Analyzed the regulation of these E3 ligases by Hh pathway components and other signaling cascades.
Main Results:
- Ubiquitination of Gli proteins leads to their proteasomal degradation or cleavage, effectively downregulating Hh signaling.
- Specific E3 ligases, regulated by pathway components like Smo-activated kinases and Itch, control Gli ubiquitination.
- These ubiquitination events suppress Gli function, directly or indirectly impacting downstream targets like HDAC1.
Conclusions:
- Gli ubiquitination is a key regulatory mechanism that finely tunes Hh signaling during development.
- Dysregulation of these ubiquitination processes contributes to tumorigenesis.
- Targeting Gli ubiquitination pathways presents a promising strategy for novel cancer therapies.
Related Concept Videos
02:33Hedgehog Signaling Pathway
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
02:33Hedgehog Signaling Pathway
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
02:04Covalently 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.
These groups modify specific amino acids in a protein.
02:58Regulated 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...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
02:58Regulated 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...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
02:32Histone Modification
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...