The retinoblastoma gene is involved in multiple aspects of stem cell biology

Abstract

Genetic programs controlling self-renewal and multipotentiality of stem cells have overlapping pathways with cell cycle regulation. Components of cell cycle machinery can play a key role in regulating stem cell self-renewal, proliferation, differentiation and aging. Among the negative regulators of cell cycle progression, the RB family members play a prominent role in controlling several aspects of stem cell biology. Stem cells contribute to tissue homeostasis and must have molecular mechanisms that prevent senescence and hold 'stemness'. RB can induce senescence-associated changes in gene expression and its activity is downregulated in stem cells to preserve self-renewal. Several reports evidenced that RB could play a role in lineage specification of several types of stem cells. RB has a role in myogenesis as well as in cardiogenesis. These effects are not only related to its role in suppressing E2F-responsive genes but also to its ability to modulate the activity of tissue-specific transcription factors. RB is also involved in adipogenesis through a strict control of lineage commitment and differentiation of adipocytes as well in determining the switch between brown and white adipocytes. Also, hematopoietic progenitor cells utilize the RB pathway to modulate cell commitment and differentiation. In this review, we will also discuss the role of the other two RB family members: Rb2/p130 and p107 showing that they have both specific and overlapping functions with RB gene.

The BRG1 ATPase of chromatin remodeling complexes is involved in modulation of mesenchymal stem cell senescence through RB–P53 pathways

“…RB and P53 pathways are involved in biological effects induced by BRG1 silencing RB and P53 pathways are part of the core circuitry that controls cell cycle arrest, differentiation, apoptosis and/or senescence (Galderisi et al, 2006;Campisi and d'Adda di Fagagna, 2007;Oberdoerffer and Sinclair, 2007). Several reports showed that BRG1 operates through regulation of these key cellular pathways (Strobeck et al, 2000;Lee et al, 2002;Hendricks et al, 2004;Kang et al, 2004).…”

“…In fact, the H2AX activation and the upregulation in the expression BRG1, RB and P53 crosstalk Several reports suggested that BRG1 binds to and regulates the retinoblastoma protein and the tumor suppressor protein p53 (Strobeck et al, 2000;Lee et al, 2002;Hendricks et al, 2004;Kang et al, 2004). These are master genes that control cell cycle arrest, differentiation, apoptosis and/or senescence (Felsani et al, 2006;Galderisi et al, 2006;Campisi and d'Adda di Fagagna, 2007;Oberdoerffer and Sinclair, 2007). We tried to evaluate whether the biological effects of BRG1 silencing were related to RB-and P53-related pathways.…”

Mesenchymal stromal cells having inactivated RB1 survive following low irradiation and accumulate damaged DNA: Hints for side effects following radiotherapy

“…13,14 On the contrary, our previous findings demonstrated that MSC lacking RB1 expression showed a decline in proliferation and accumulation of DNA damage. This impairs stem cell properties with an increase in senescence.…”

“…This is in contrast with reports of other cell types including fibroblasts that showed strong resistance to cell cycle exit and uncontrolled proliferation following RB1 ablation. 13,14 Nevertheless, there are findings showing that RB1 may be dispensable for cell cycle exit and control of cell growth because it occurs in cardiomyocytes and pancreatic ß-cells. 19,20 Altogether these studies clearly show that RB1 function is context dependent, in some settings RB1, RB2/P130, and P107 can compensate for each other.…”

Retinoblastoma protein and the leukemia-associated PLZF transcription factor interact to repress target gene promoters

“…Although Rb is involved in multiple aspects of stem cell biology (Galderisi et al, 2006), its contribution in early hematopoiesis remains unclear. For example, it has been reported that Rb is dispensable for self-renewal and multilineage differentiation of adult hematopoietic stem cells (Walkley and Orkin, 2006).…”