Cbx4 Sumoylates Prdm16 to Regulate Adipose Tissue Thermogenesis
Qingbo Chen1, Lei Huang1, Dongning Pan2
1Department of Molecular, Cell and Cancer Biology and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Cell Reports
|March 15, 2018
Summary
Polycomb protein Cbx4 stabilizes the brown fat regulator Prdm16 through sumoylation, enhancing thermogenic gene expression and promoting white fat browning. This finding reveals a key mechanism controlling energy expenditure.
Area of Science:
- Cellular and Molecular Biology
- Metabolic Regulation
- Epigenetics
Background:
- Prdm16 is crucial for brown adipose tissue development and white fat browning.
- Post-translational modifications of Prdm16 that regulate its function are not well understood.
Purpose of the Study:
- To investigate the post-translational regulation of Prdm16.
- To identify the role of Cbx4 in modulating Prdm16 activity and adipose tissue thermogenesis.
Main Methods:
- Biochemical assays to determine Cbx4's E3 ligase activity for Prdm16.
- Analysis of Prdm16 sumoylation, ubiquitination, and degradation.
- Gene expression analysis of thermogenic markers.
- Phenotypic analysis of Cbx4-knockout and knockdown/overexpression mouse models.
Main Results:
- Cbx4 acts as a SUMO E3 ligase for Prdm16, mediating its sumoylation at lysine 917.
- Cbx4-mediated sumoylation stabilizes Prdm16 by preventing its ubiquitination-mediated degradation.
- Sumoylated Prdm16 is essential for thermogenic gene expression and primes Prdm16 for further stabilization by Ehmt1.
- Cbx4 deficiency in mice leads to metabolic phenotypes similar to Prdm16 deficiency, and Cbx4 manipulation affects white fat remodeling.
Conclusions:
- Cbx4 is a critical regulator of Prdm16 stability and function through sumoylation.
- Cbx4 plays a central role in controlling adipose tissue thermogenesis and white fat browning.
- This study uncovers a novel regulatory pathway for thermogenic adaptation.
Related Concept Videos
01:46Epigenetic Regulation
33.9K
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
33.9K
02:14GTPases and their Regulation
9.9K
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,...
Large G-proteins,...
9.9K
02:23Master Transcription Regulators
7.8K
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...
7.8K
02:58Regulated Protein Degradation
8.9K
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...
8.9K
01:23Negative Regulator Molecules
38.6K
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.
38.6K
01:45Positive Regulator Molecules
136.5K
To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
136.5K