Related Experiment Video
Updated: Nov 8, 2025
08:34
Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
Published on: June 3, 2016
15.4K
Ubiquitin specific peptidase Usp53 regulates osteoblast versus adipocyte lineage commitment
Hadla Hariri1,2, William N Addison1, René St-Arnaud3,4,5,6
1Research Centre, Shriners Hospital for Children - Canada, 1003 Decarie Boulevard, Montreal, QC, H4A 0A9, Canada.
Scientific Reports
|April 20, 2021
Summary
Parathyroid hormone (PTH) activates Nascent polypeptide-associated complex And Coregulator alpha (NACA), which targets Ubiquitin Specific Peptidase 53 (Usp53) in osteoblasts. Usp53 knockdown promotes osteoblast differentiation and impacts mesenchymal cell fate.
Area of Science:
- Molecular Biology
- Cell Biology
- Bone Biology
Background:
- Parathyroid hormone (PTH) signaling is crucial for bone metabolism.
- Nascent polypeptide-associated complex And Coregulator alpha (NACA) is a DNA-binding protein regulated by PTH.
- Understanding NACA's downstream targets is key to elucidating PTH's effects on bone cells.
Purpose of the Study:
- To identify target genes of PTH-activated NACA in osteoblasts.
- To investigate the role of Ubiquitin Specific Peptidase 53 (Usp53) in osteoblast differentiation and mesenchymal cell fate.
- To elucidate the regulatory mechanism of Usp53 gene expression.
Main Methods:
- ChIP-Sequencing (ChIP-Seq) and RNA-sequencing were used to identify NACA target genes.
- Electrophoretic mobility shift assay (EMSA) confirmed NACA binding to the Usp53 promoter.
- Gene knockdown (Usp53 and Naca) in cell culture and in vivo mouse models.
Main Results:
- Ubiquitin Specific Peptidase 53 (Usp53) was identified as a direct target gene of PTH-activated NACA.
- Usp53 promoter activity is regulated by the JUN-CREB complex, PKA, and NACA.
- Usp53 knockdown promoted osteoblast differentiation and inhibited adipogenesis in mesenchymal stromal cells.
- Usp53 knockdown enhanced osteoblast numbers and reduced adipocyte counts in vivo.
Conclusions:
- Usp53 is a novel target gene of PTH-NACA signaling in osteoblasts.
- Usp53 plays a critical role in regulating mesenchymal stem cell lineage commitment towards osteoblasts.
- Usp53 modulation impacts bone formation and may represent a therapeutic target for bone diseases.
Related Concept Videos
02:58Regulated Protein Degradation
8.0K
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...
8.0K
02:23Abnormal Proliferation
4.8K
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
02:04Covalently Linked Protein Regulators
8.1K
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....
8.1K
01:21Lineage Commitment
3.6K
Commitment is the process whereby stem cells:
3.6K
01:31Regulation of the Unfolded Protein Response
2.8K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.8K
01:58Cell Specific Gene Expression
14.5K
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
14.5K