RBF1 promotes chromatin condensation through a conserved interaction with the Condensin II protein dCAP-D3
Open accessAbstract
The Drosophila retinoblastoma family of proteins (RBF1 and RBF2) and their mammalian homologs (pRB, p130, and p107) are best known for their regulation of the G1/S transition via the repression of E2F-dependent transcription. However, RB family members also possess additional functions. Here, we report that rbf1 mutant larvae have extensive defects in chromatin condensation during mitosis. We describe a novel interaction between RBF1 and dCAP-D3, a non-SMC component of the Condensin II complex that links RBF1 to the regulation of chromosome structure. RBF1 physically interacts with dCAP-D3, RBF1 and dCAP-D3 partially colocalize on polytene chromosomes, and RBF1 is required for efficient association of dCAP-D3 with chromatin. dCap-D3 mutants also exhibit chromatin condensation defects, and mutant alleles of dCap-D3 suppress cellular and developmental phenotypes induced by the overexpression of RBF1. Interestingly, this interaction is conserved between flies and humans. The re-expression of pRB into a pRB-deficient human tumor cell line promotes chromatin association of hCAP-D3 in a manner that depends on the LXCXE-binding cleft of pRB. These results uncover an unexpected link between pRB/RBF1 and chromatin condensation, providing a mechanism by which the functional inactivation of RB family members in human tumor cells may contribute to genome instability.
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RB may normally promote chromosomal condensation and preserve chromosomal stability through direct interaction with condensin.
“Recent experiments in Drosophila melanogaster and human cells also indicate that RB might normally promote chromosomal condensation and preserve chromosomal stability through a direct interaction with a condensin protein115.”
From Cellular mechanisms of tumour suppression by the retinoblastoma gene (2008) · cites this paper as [115]
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- Authors
- Longworth, M. S., Herr, A., Ji, J.-Y., & Dyson, N. J.
- Affiliations
- Harvard University (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2008-03-26
- Volume
- 22
- Issue
- 8
- Pages
- 1011-1024
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC2335323
- OpenAlex
- W2113239433
- Cited by
- 122
- References
- 10
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 5 · 2022: 5 · 2021: 7 · 2020: 7 · 2019: 6 · 2018: 6 · 2017: 8 · 2016: 4 · 2015: 4 · 2014: 8 · 2013: 16 · 2012: 14
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Leukemia and Lymphoma Society
- Exelixis
- National Institutes of Health
- National Cancer Institute (CA64402, R01CA064402)
- National Institute of General Medical Sciences (GM-53203, R01GM053203)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- Rbf1, retinoblastoma protein family, condensin II, chromatin condensation, mitosis, polytene chromosomes, protein-protein interaction, retinoblastoma protein, genomic instability, Drosophila, human cancer cells
- MeSH terms
- Adenosine Triphosphatases, Animals, Cells, Cultured, Chromatin, DNA-Binding Proteins, Humans, Larva, Microscopy, Fluorescence, Models, Biological, Neoplasms, Transcription Factors, Retinoblastoma Protein, Drosophila Proteins, Cell Line, Tumor, Multiprotein Complexes
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