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Cited by 100Telomeres, Telomerase, and SenescenceCancer-related Molecular PathwaysRetinal Development and Disorders

Role of the Retinoblastoma Protein in Differentiation and Senescence

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Thomas, David M., Yang, Hai-Su, Alexander, Kamilah, Hinds, Philip W.·2003·Cancer Biology & Therapy
DOI 10.4161/cbt.2.2.235
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Abstract

The retinoblastoma protein pRb is functionally inactivated in most human cancers. Numerous studies in cell culture and animal models suggest that pRb has a unique ability to encourage and enforce permanent cell cycle withdrawal, consistent with its role as a tumor suppressor protein. This cell cycle withdrawal has a generic component involving repression of transcription of genes required for proliferation. In addition, numerous studies hint at additional specific roles for pRb in differentiation of certain tissue types. Further, pRb appears to play a central role in the process of cellular senescence, a tumorsuppressive process characterized by proliferative arrest and phenotypic changes. Both differentiation and senescence pathways influenced by pRb involve direct and indirect interactions with the core machinery involved in cell-type-specific differentiation and cell shape control. This review focuses on pRb's role as an participant in osteoblast differentiation illustrative of a broader role in terminal differentiation. In addition, novel pathways activated by pRb in its role as an inducer of cellular senescence will be discussed.

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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 [60]

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Authors
Thomas, D. M., Yang, H.-S., Alexander, K., & Hinds, P. W.
Affiliations
  • The University of Melbourne (AU)
  • Harvard University (US)
ORCID
Venue
Cancer Biology & Therapy
Publisher
Informa UK Limited
Published
2003-03
Volume
2
Issue
2
Pages
124-130
ISSN
  • 1538-4047 (ISSN-L)
  • 1555-8576
DOI
10.4161/cbt.2.2.235
OpenAlex
W2335445771
Cited by
100
References
0
Citations by year
2025: 1 · 2022: 2 · 2021: 2 · 2019: 1 · 2018: 1 · 2017: 3 · 2016: 6 · 2015: 3 · 2014: 5 · 2013: 7 · 2012: 4
FWCI
6.32
Type
journal article
Language
en
Open access
Locations
  • Cancer Biology & Therapy (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Public Health Service
  • National Institute on Aging (R01AG020208, AG20208)
  • National Cancer Institute (1U01CA91178-01)
Topics
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
Keywords
retinoblastoma protein, cell cycle withdrawal, cellular senescence, cell differentiation, osteogenic differentiation, terminal differentiation, tumor suppressor, proliferative arrest, transcriptional repression
MeSH terms
Animals, Cell Differentiation, Humans, Neoplasms, Osteoblasts, Retinoblastoma Protein, Cellular Senescence

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