Role of RB family on senescence
Studies on senescence induced by chromatin remodelling factors and Retinoblastoma gene family members.
We have focused our attention on self-renewal, proliferation, senescence and differentiation of stem cells. Their activity is regulated by chromatin remodelling factors that operate at the highest hierarchical level. Studies on these factors can be especially important to dissect molecular pathways governing the biology of stem cells.
SWI/SNF complexes are ATP-dependent chromatin remodelling enzymes that have been shown to be required for cell cycle control, apoptosis and cell differentiation in several biological systems. The aim of our research is to investigate the role of these complexes in the biology of MSCs in particular by silencing the catalytic SWI/SNF subunit called BRG1.
SWI/SNF complexes accomplish their tasks also by interacting with members of the retinoblastoma gene family.
The retinoblastoma family genes RB1, RB2/P130, and P107 play a major role in controlling the cell cycle G1 /S transition through the negative regulation of the E2F family of transcription factors. In addition, this protein family plays an important role in regulating other cellular processes, such as terminal differentiation and senescence. Initial observations suggested that retinoblastoma family proteins showed overlapping functions, and initial knock-out studies suggested that Rb2/p130 and p107 had an ancillary role. However, several studies have evidenced functional differences among these proteins. Recently, it has become clear that the role of Rb1, Rb2/p130, and p107 depends on several parameters such as animal species under investigation, cell type, and cell status (stem cell, progenitor, differentiated cell). Data on the function of retinoblastoma family members in the control of stem cell biology have been biased by the fact that the majority of authors have focused their attention mainly on the Rb1 protein. Data on the role of p107 and Rb2/p130 in stem cell biology are very scant.
Moreover, the functions of Rb1, p107, and Rb2/p130 in the biology of mesenchymal stem cells (MSCs) remain largely uncharacterized. These cells contribute significantly to the maintenance of tissue homeostasis in the body.
Consequently, any loss in numbers or the functionality of MSCs would have profound consequences for the maintenance of tissue viability. In-depth studies on the biology of MSCs also have a great therapeutic value since they are being tested in cell and gene therapy for a number of human diseases.
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