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Scientific result | Molecular mechanisms | Cellular mechanisms
A team from the Innovative Therapies Unit (STI) has discovered a molecular mechanism that regulates the balance between white and brown fat. Their work defines a novel category of potential targets in the quest to control fat mass.
What drives cells to either multiply or differentiate? The balance between these two pathways is finely regulated by the control of interactions between the proteins involved in those two destinies. As concerns adipose tissue formation (adipogenesis), a study performed by a team from the François Jacob Institute of Biology's Department of Innovative Therapies (STI) suggests that interactions between two proteins, FOG-2 and pRb, control adipose tissue differentiation, either to white fat for lipid stocking or brown fat for thermogenesis. The study hints at new possibilities for the prevention of adipose tissue pathologies such as obesity.
The research team, headed by Stany Chrétien, has long focused on two protein families: the transcription factors GATA and their cofactors FOG ("friends of GATA"). Both play essential roles in tissue differentiation by regulating the expression of numerous genes. The team has already shown that the production and maturation of red blood cells is controlled by a dynamic equilibrium of interactions between GATA-1 and FOG-1 or pRb, this latter being a protein that stops the cell cycle (see "Une voie de secours pour produire des globules rouges", article in French).
More recently, they have directed their attention to FOG-2, a protein known to have a role in adipogenesis, and succeeded in identifying a peptide motif in it, called LXCXE, which enables FOG-2 to interact with pRb, like GATA-1 can. The team developed a murine model to evaluate the consequences of the absence of the LXCXE motif from FOG-2. The animals with the mutated FOG-2 showed hyperactivity and increased resistance to cold and obesity: their white fat was partially converted to brown fat. In cultured adipocyte precursor cells, the team also demonstrated that the mutated FOG-2 slowed the cell cycle, deregulated the expression of several genes involved in cell cycle control and ultimately disturbed the proliferation of the cells.
The LXCXE Retinoblastoma Protein-binding Motif
of FOG-2 Regulates Adipogenesis | Cell Reports
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