RB, the conductor that orchestrates life, death and differentiation

Abstract

The retinoblastoma susceptibility gene was the first tumor suppressor gene identified in humans and the first tumor suppressor gene knocked out by targeted deletion in mice. RB serves as a transducer between the cell cycle machinery and promoter-specific transcription factors, its most documented activity being the repression of the E2F family of transcription factors, which regulate the expression of genes involved in cell proliferation and survival. Recent investigations of RB function suggest that it works as a fundamental regulator to coordinate pathways of cellular growth and differentiation. In this review, we unravel the novel role of an equally important aspect of RB in downregulating the differentiation inhibitor EID-1 during cellular differentiation by teasing apart the signal, which elicit differentiation and limit cell cycle progression, since the molecular mechanisms relating to RB activation of differentiation is much less understood. We review the various roles for RB in differentiation of neurons, muscle, adipose tissue, and the retina. In addition, we provide an update for the current models of the role of RB in cell cycle to entry and exit, extending the view toward chromatin remodeling and expose the dichotomies in the regulation of RB family members. We conclude with a discussion of a novel RB regulatory network, incorporating the dynamic contribution of EID family proteins.

Aberrant nucleocytoplasmic localization of the retinoblastoma tumor suppressor protein in human cancer correlates with moderate/poor tumor differentiation

“…Differentiation and cancer: the role of RB RB regulates cellular differentiation and survival (Goodrich, 2006;Khidr and Chen, 2006) and promotes differentiation and development of neural cells, skeletal muscle cells, retinal cells and adipocytes (Khidr and Chen, 2006). It is plausible that inactivation of RB during cancer progression may inhibit normal differentiation processes and allow cells to aberrantly remain in the cell cycle and undergo cell division.…”

Diversity within the pRb pathway: is there a code of conduct?

“…For example, the role of pRb is well established in myogenesis, osteogenesis, adipogenesis and neurogenesis (Khidr and Chen, 2006). Elevated levels of acetylated pRb are observed during differentiation (Chan et al, 2001a;Nguyen et al, 2004;Pickard et al, 2010).…”

Bortezomib decreases Rb phosphorylation and induces caspase-dependent apoptosis in Imatinib-sensitive and -resistant Bcr-Abl1-expressing cells

“…Btz treatment reduces the phosphorylation and the activity of Rb in Bcr-Abl1-expressing cells At the molecular level, Rb phosphorylation regulates the transition from G1 into S phase (Khidr and Chen, 2006). Therefore, we analyzed the effect of Btz on the phosphorylation status of Rb by western blot.…”