ArticlePLoS biology2013
The ING1a tumor suppressor regulates endocytosis to induce cellular senescence via the Rb-E2F pathway.
Article in PLoS biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Rab22a is a novel prognostic marker for cell progression in breast cancer.International journal of molecular medicine · 2020Trial
- A recently evolved domain of the human ING1 epigenetic regulator targets mitochondria and induces senescence.Cellular and molecular life sciences : CMLS · 2026Article
- Predicting the Impact of Deleterious Single-Nucleotide Polymorphisms in the p47ING1a Isoform of Human ING1 Gene.Genetics research · 2026Article
- Therapy-induced senescence in breast cancer: an overview.Exploration of targeted anti-tumor therapy · 2024Review
- Review
- Altered endocytosis in cellular senescence.Ageing research reviews · 2021Review
- Integrin-mediated adhesions in regulation of cellular senescence.Science advances · 2020Article
- Senescence and Apoptosis: Architects of Mammalian Development.Frontiers in cell and developmental biology · 2020Review
- Focus-ING on DNA Integrity: Implication of ING Proteins in Cell Cycle Regulation and DNA Repair Modulation.Cancers · 2019Review
- miR-135b-5p enhances doxorubicin-sensitivity of breast cancer cells through targeting anterior gradient 2.Journal of experimental & clinical cancer research : CR · 2019Article
- Senolytics: A Translational Bridge Between Cellular Senescence and Organismal Aging.Frontiers in cell and developmental biology · 2019Review
- ING5 activity in self-renewal of glioblastoma stem cells via calcium and follicle stimulating hormone pathways.Oncogene · 2018Article
- ING1 regulates rRNA levels by altering nucleolar chromatin structure and mTOR localization.Nucleic acids research · 2017Article
- INGs are potential drug targets for cancer.Journal of cancer research and clinical oncology · 2017Review
- Identification of cellular senescence-specific genes by comparative transcriptomics.Scientific reports · 2016Article
- Aging with ING: a comparative study of different forms of stress induced premature senescence.Oncotarget · 2015Article
- LincRNA-p21 acts as a mediator of ING1b-induced apoptosis.Cell death & disease · 2015Article
- SUMOylation of the ING1b tumor suppressor regulates gene transcription.Carcinogenesis · 2014Article
- Truncation of inhibitor of growth family protein 5 effectively induces senescence, but not apoptosis in human tongue squamous cell carcinoma cell line.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- Senescence: ConnectING endocytosis.Nature reviews. Cancer · 2013Article
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3 authors at 1 institution in 1 country.
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Abstract
The INhibitor of Growth (ING) proteins act as type II tumor suppressors and epigenetic regulators, being stoichiometric members of histone acetyltransferase and histone deacetylase complexes. Expression of the alternatively spliced ING1a tumor suppressor increases >10-fold during replicative senescence. ING1a overexpression inhibits growth; induces a large flattened cell morphology and the expression of senescence-associated β-galactosidase; increases Rb, p16, and cyclin D1 levels; and results in the accumulation of senescence-associated heterochromatic foci. Here we identify ING1a-regulated genes and find that ING1a induces the expression of a disproportionate number of genes whose products encode proteins involved in endocytosis. Intersectin 2 (ITSN2) is most affected by ING1a, being rapidly induced >25-fold. Overexpression of ITSN2 independently induces expression of the p16 and p57(KIP2) cyclin-dependent kinase inhibitors, which act to block Rb inactivation, acting as downstream effectors of ING1a. ITSN2 is also induced in normally senescing cells, consistent with elevated levels of ING1a inducing ITSN2 as part of a normal senescence program. Inhibition of endocytosis or altering the stoichiometry of endosome components such as Rab family members similarly induces senescence. Knockdown of ITSN2 also blocks the ability of ING1a to induce a senescent phenotype, confirming that ITSN2 is a major transducer of ING1a-induced senescence signaling. These data identify a pathway by which ING1a induces senescence and indicate that altered endocytosis activates the Rb pathway, subsequently effecting a senescent phenotype.
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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.