ArticleMolecular and cellular biology2012
TIN2 stability is regulated by the E3 ligase Siah2.
Article in Molecular and cellular biology, 2012. 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, 28 citations in OpenAlex.
- Structural biology of shelterin and telomeric chromatin: the pieces and an unfinished puzzle.Biochemical Society transactions · 2024Review
- Molecular mechanisms of aging and anti-aging strategies.Cell communication and signaling : CCS · 2024Review
- Molecular insight of dyskeratosis congenita: Defects in telomere length homeostasis.Journal of clinical and translational research · 2022Review
- Shaping human telomeres: from shelterin and CST complexes to telomeric chromatin organization.Nature reviews. Molecular cell biology · 2021Review
- Naked mole rat TRF1 safeguards glycolytic capacity and telomere replication under low oxygen.Science advances · 2021Article
- The Role of Ubiquitination and SUMOylation in Telomere Biology.Current issues in molecular biology · 2020Review
- Condensin II subunit NCAPH2 associates with shelterin protein TRF1 and is required for telomere stability.Journal of cellular physiology · 2019Article
- TIN2 Functions with TPP1/POT1 To Stimulate Telomerase Processivity.Molecular and cellular biology · 2019Article
- Effects of TIN2 on telomeres and chromosomes in the human gastric epithelial cell line GES-1.Oncology letters · 2018Article
- Antagonizing functions of BARD1 and its alternatively spliced variant BARD1δ in telomere stability.Oncotarget · 2017Article
- Seven in Absentia E3 Ubiquitin Ligases: Central Regulators of Neural Cell Fate and Neuronal Polarity.Frontiers in cellular neuroscience · 2017Review
- Ubiquitination and SUMOylation in Telomere Maintenance and Dysfunction.Frontiers in genetics · 2017Review
- Molecular basis of telomere dysfunction in human genetic diseases.Nature structural & molecular biology · 2015Review
- Telomere-regulating genes and the telomere interactome in familial cancers.Molecular cancer research : MCR · 2015Review
- Central role of SIAH inhibition in DCC-dependent cardioprotection provoked by netrin-1/NO.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Regulators and effectors of Siah ubiquitin ligases.Cell biochemistry and biophysics · 2013Review
- p300-mediated acetylation of TRF2 is required for maintaining functional telomeres.Nucleic acids research · 2013Article
- Article
- Chromatin structure in telomere dynamics.Frontiers in oncology · 2013Article
- Fusing telomeres with RNF8.Nucleus (Austin, Tex.) · 2012Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Telomeres are coated by shelterin, a six-subunit complex that is required for protection and replication of chromosome ends. The central subunit TIN2, with binding sites to three subunits (TRF1, TRF2, and TPP1), is essential for stability and function of the complex. Here we show that TIN2 stability is regulated by the E3 ligase Siah2. We demonstrate that TIN2 binds to Siah2 and is ubiquitylated in vivo. We show using purified proteins that Siah2 acts as an E3 ligase to directly ubiquitylate TIN2 in vitro. Depletion of Siah2 led to stabilization of TIN2 protein, indicating that Siah2 regulates TIN2 protein levels in vivo. Overexpression of Siah2 in human cells led to loss of TIN2 at telomeres that was dependent on the presence of the catalytic RING domain of Siah2. In contrast to RNAi-mediated depletion of TIN2 that led to loss of TRF1 and TRF2 at telomeres, Siah2-mediated depletion of TIN2 allowed TRF1 and TRF2 to remain on telomeres, indicating a different fate for shelterin subunits when TIN2 is depleted posttranslationally. TPP1 was lost from telomeres, although its protein level was not reduced. We speculate that Siah2-mediated removal of TIN2 may allow dynamic remodeling of the shelterin complex and its associated factors during the cell cycle.
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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.