Pocket proteins and cell cycle control
Abstract
The retinoblastoma protein (pRB) and the pRB-related p107 and p130 comprise the 'pocket protein' family of cell cycle regulators. These proteins are best known for their roles in restraining the G1-S transition through the regulation of E2F-responsive genes. pRB and the p107/p130 pair are required for the repression of distinct sets of genes, potentially due to their selective interactions with E2Fs that are engaged at specific promoter elements. In addition to regulating E2F-responsive genes in a reversible manner, pocket proteins contribute to silencing of such genes in cells that are undergoing senescence or differentiation. Pocket proteins also affect the G1-S transition through E2F-independent mechanisms, such as by inhibiting Cdk2 or by stabilizing p27(Kip1), and they are implicated in the control of G0 exit, the spatial organization of replication, and genomic rereplication. New insights into pocket protein regulation have also been obtained. Kinases previously thought to be crucial to pocket protein phosphorylation have been shown to be redundant, and new modes of phosphorylation and dephosphorylation have been identified. Despite these advances, much remains to be learned about the pocket proteins, particularly with regard to their developmental and tumor suppressor functions. Thus continues the story of the pocket proteins and the cell cycle.
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RB belongs to a family with p107 and p130, which are structurally and functionally related, share the same pathway, but have distinct functions in specific contexts.
“In mammalian cells, RB belongs to a family of three proteins that also includes p107 and p130, which are structurally and functionally related to RB and belong to the same cellular pathway, but display distinct functions from RB in specific contexts4,7–10”
From Cellular mechanisms of tumour suppression by the retinoblastoma gene (2008) · cites this paper as [8]
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- Authors
- Cobrinik, D.
- Affiliations
- Cornell University (US)
- Corresponding author
- Cobrinik, David
- ORCID
- Cobrinik, David
- Venue
- Oncogene
- Published
- 2005-04-18
- Volume
- 24
- Issue
- 17
- Pages
- 2796-2809
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2065906581
- Cited by
- 601
- References
- 16
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 8 · 2023: 17 · 2022: 16 · 2021: 25 · 2020: 13 · 2019: 11 · 2018: 16 · 2017: 16 · 2016: 26 · 2015: 29 · 2014: 31 · 2013: 46 · 2012: 49
- FWCI
- 5.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Starr Foundation
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- pocket proteins, retinoblastoma protein, p107, p130, cell cycle regulation, G1/S transition, CDK2 inhibition, p27, senescence, cell differentiation, protein phosphorylation, tumor suppressor function
- MeSH terms
- Cell Cycle, DNA Replication, DNA-Binding Proteins, Humans, Nuclear Proteins, Proteins, Transcription Factors, Retinoblastoma Protein, Cell Cycle Proteins, Cyclin E, E2F Transcription Factors, Retinoblastoma-Like Protein p130, Retinoblastoma-Like Protein p107
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