ArticleOncogene2008
Aberrant nucleocytoplasmic localization of the retinoblastoma tumor suppressor protein in human cancer correlates with moderate/poor tumor differentiation.
Article in Oncogene, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
22 citing papers in PubMed, 51 citations in OpenAlex.
- Deep generative model for protein subcellular localization prediction.Briefings in bioinformatics · 2025Article
- Non-catalytic allostery in α-TAT1 by a phospho-switch drives dynamic microtubule acetylation.The Journal of cell biology · 2022Article
- Cross-regulation of viral kinases with cyclin A secures shutoff of host DNA synthesis.Nature communications · 2020Article
- BRCA1 subcellular localization regulated by PI3K signaling pathway in triple-negative breast cancer MDA-MB-231 cells and hormone-sensitive T47D cells.Open life sciences · 2020Article
- Immunohistochemical detection of p53, PTEN, Rb, and p16 in canine osteosarcoma using tissue microarray.Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc · 2018Article
- Inhibition of Rb Phosphorylation Leads to mTORC2-Mediated Activation of Akt.Molecular cell · 2016Article
- Pancreatic adenocarcinoma up-regulated factor expression is associated with disease-specific survival in cervical cancer patients.Human pathology · 2015Article
- Identification and characterization of nuclear and nucleolar localization signals in 58-kDa microspherule protein (MSP58).Journal of biomedical science · 2015Article
- Telomere dysfunction suppresses multiple endocrine neoplasia in mice.Genes & cancer · 2014Article
- Protein mislocalization: mechanisms, functions and clinical applications in cancer.Biochimica et biophysica acta · 2014Review
- Cytoplasmic translocation of the retinoblastoma protein disrupts sarcomeric organization.eLife · 2013Article
- The retinoblastoma protein induces apoptosis directly at the mitochondria.Genes & development · 2013Article
- Synaptonemal complex protein 3 as a novel prognostic marker in early stage non-small cell lung cancer.Human pathology · 2013Article
- Inactivation of Rb in stromal fibroblasts promotes epithelial cell invasion.The EMBO journal · 2012Article
- RB116: an RB1+ retinoblastoma cell line expressing primitive markers.Molecular vision · 2012Article
- Acetylation of Rb by PCAF is required for nuclear localization and keratinocyte differentiation.Journal of cell science · 2010Article
- p27(Kip1), a double-edged sword in Shh-mediated medulloblastoma: Tumor accelerator and suppressor.Cell cycle (Georgetown, Tex.) · 2010Article
- Identification and functional analysis of NOL7 nuclear and nucleolar localization signals.BMC cell biology · 2010Article
- Nucleo-cytoplasmic localization domains regulate Krüppel-like factor 6 (KLF6) protein stability and tumor suppressor function.PloS one · 2010Article
- Evidence for a mitochondrial localization of the retinoblastoma protein.BMC cell biology · 2009Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Inactivation of the retinoblastoma (RB) tumor suppressor pathway, via elevated cyclin-dependent kinase (CDK) activity, is observed in majority of human cancers. Since CDK deregulation is evident in most cancer cells, pharmacological CDK inhibition has become an attractive therapeutic strategy in oncology. We recently showed that an oncogenic CDK4(R24C) mutation alters the subcellular localization of the normally nuclear RB phosphoprotein. Here, using 71 human cancer cell lines and over 300 primary human cancer tissues, we investigated whether changes in RB subcellular localization occur during human cancer progression. We uncover that diverse human cancers and their derived cell lines, particularly those with poor tumor differentiation, display significant cytoplasmic mislocalization of ordinarily nuclear RB. The nucleocytoplasmically distributed RB was derived via CDK-dependent and Exportin1-mediated nuclear export. Indeed, cytoplasmically mislocalized RB could be efficiently confined to the nucleus by pharmacologically reducing CDK activity or by inhibiting the Exportin1-mediated nuclear export pathway. Our observations uncover a post-translational CDK-dependent mechanism of RB inactivation and suggest that cytoplasmically localized RB may harbor a tumor promoting function. We propose that RB inactivation, via aberrant nucleocytoplasmic transport, may disrupt normal cell differentiation programs and accelerate the cancer process. These results are evidence that tumor cells modulate the protein transport machinery thereby making the protein transport process a viable therapeutic target.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.