Cited by 79Cancer-related Molecular PathwaysChromatin Remodeling and CancerGenomics and Chromatin Dynamics

Structure-function analysis of the retinoblastoma tumor suppressor protein – is the whole a sum of its parts?

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Dick, Frederick A·2007·Cell Division

Abstract

Biochemical analysis of the retinoblastoma protein's function has received considerable attention since it was cloned just over 20 years ago. During this time pRB has emerged as a key regulator of the cell division cycle and its ability to block proliferation is disrupted in the vast majority of human cancers. Much has been learned about the regulation of E2F transcription factors by pRB in the cell cycle. However, many questions remain unresolved and researchers continue to explore this multifunctional protein. In particular, understanding how its biochemical functions contribute to its role as a tumor suppressor remains to be determined. Since pRB has been shown to function as an adaptor molecule that links different proteins together, or to particular promoters, analyzing pRB by disrupting individual protein interactions holds tremendous promise in unraveling the intricacies of its function. Recently, crystal structures have reported how pRB interacts with some of its molecular partners. This information has created the possibility of rationally separating pRB functions by studying mutants that disrupt individual binding sites. This review will focus on literature that investigates pRB by isolating functions based on binding sites within the pocket domain. This article will also discuss the prospects for using this approach to further explore the unknown functions of pRB.

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Crossref · 10.1186/1747-1028-2-26

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  • Among the E2F family, apoptosis induction is largely mediated by E2F1, and its repression by RB involves domains distinct from those controlling cell cycle progression.

    “among the E2F family, induction of apoptosis is a function largely mediated by E2F1 and its repression is mediated by specific RB and E2F1 protein domains that are distinct from those through which RB interacts with E2F1, E2F2, E2F3 and E2F4 to control cell cycle progression78.”
  • Ectopic RB expression in cultured cells can have nonspecific effects.

    “Similarly, because ectopic expression of RB in cells in culture can produce nonspecific effects, a detailed structure–function analysis of RB in vivo will be key to our understanding of RB tumour suppressor functions78.”

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  1. Dunaief JL Strober BE Guha S Khavari PA Alin K Luban J Begemann M Crabtree GR Goff SP The retinoblastoma protein and BRG1 form a complex and cooperate to induce cell cycle arrest. Cell 1994 79 119 30 7923370 10.1016/0092-8674(94)90405-7 · DOI

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Authors
Dick, F. A.
Affiliations
Western University (CA)
Corresponding author
Dick, Frederick A
Venue
Cell Division
Published
2007
Volume
2
Issue
1
Pages
26
ISSN
1747-1028 (ISSN-L)
OpenAlex
W2164026919
Cited by
79
References
176
Citations by year
2025: 2 · 2024: 4 · 2023: 2 · 2022: 2 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 7 · 2015: 5 · 2014: 7 · 2013: 11 · 2012: 13
FWCI
2.06
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Cell Division (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Canadian Institutes of Health Research (MOP64253)
  • National Cancer Institute
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 › Genomics and Chromatin Dynamics
Keywords
retinoblastoma protein, tumor suppressor, E2F transcription factors, cell cycle regulation, protein-protein interaction, binding sites, crystal structure, functional domains, cell proliferation

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