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.
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RB promotes cellular differentiation during embryonic development and in adult lineages.
“The role of RB in promoting cellular differentiation during embryonic development and in adult lineages has been well characterized in mutant mice and in vitro systems20,42,58–61.”
From Cellular mechanisms of tumour suppression by the retinoblastoma gene (2008) · cites this paper as [58]
Cites
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Cellular mechanisms of tumour suppression by the retinoblastoma gene
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- Authors
- Khidr, L., & Chen, P.-L.
- Affiliations
- University of California, Irvine (US)
- Corresponding author
- Chen, P-L
- Venue
- Oncogene
- Published
- 2006-08-28
- Volume
- 25
- Issue
- 38
- Pages
- 5210-5219
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2073792103
- Cited by
- 123
- References
- 15
- Citations by year
- 2024: 4 · 2023: 6 · 2022: 2 · 2021: 2 · 2020: 5 · 2019: 3 · 2018: 1 · 2017: 2 · 2016: 5 · 2015: 5 · 2014: 11 · 2013: 7 · 2012: 11
- FWCI
- 1.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Keywords
- retinoblastoma protein, tumor suppressor, E2F transcription factors, cell differentiation, cell cycle regulation, chromatin remodeling, neuronal differentiation, myogenesis, adipose tissue differentiation, retinal development
- MeSH terms
- Adipose Tissue, Animals, Cell Cycle, Cell Differentiation, Cell Division, Eye Neoplasms, Humans, Repressor Proteins, Retinoblastoma, Signal Transduction, Retinoblastoma Protein, Genes, Retinoblastoma, Cell Death, Muscle, Skeletal, Genetic Predisposition to Disease
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