دورية أكاديمية
The Tumor Suppressor ING5 Is a Dimeric, Bivalent Recognition Molecule of the Histone H3K4me3 Mark
| العنوان: | The Tumor Suppressor ING5 Is a Dimeric, Bivalent Recognition Molecule of the Histone H3K4me3 Mark |
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| المؤلفون: | Ormaza, Georgina, Rodríguez, Jhon A., Ibáñez de Okapua, Alain, Merino, Nekane, Villate, Maider, Gorroño, Irantzu, Rábano, Miriam, Palmero, Ignacio, Vilaseca, Marta, Kypta, Robert M., Vivanco, María d.M., Rojas, Adriana L., Blanco, Francisco J. |
| المساهمون: | Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Ministerio de Economía y Competitividad (España) |
| بيانات النشر: | Elsevier Academic Press |
| سنة النشر: | 2019 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| مصطلحات موضوعية: | ING5, Chromatin, NMR, Crystallography, SAXS |
| الوصف: | The INhibitor of Growth (ING) family of tumor suppressors regulates the transcriptional state of chromatin by recruiting remodeling complexes to sites with histone H3 trimethylated at lysine 4 (H3K4me3). This modification is recognized by the plant homeodomain (PHD) present at the C-terminus of the five ING proteins. ING5 facilitates histone H3 acetylation by the HBO1 complex, and also H4 acetylation by the MOZ/MORF complex. We show that ING5 forms homodimers through its N-terminal domain, which folds independently into an elongated coiled-coil structure. The central region of ING5, which contains the nuclear localization sequence, is flexible and disordered, but it binds dsDNA with micromolar affinity. NMR analysis of the full-length protein reveals that the two PHD fingers of the dimer are chemically equivalent and independent of the rest of the molecule, and they bind H3K4me3 in the same way as the isolated PHD. We have observed that ING5 can form heterodimers with the highly homologous ING4, and that two of three primary tumor-associated mutants in the N-terminal domain strongly destabilize the coiled-coil structure. They also affect cell proliferation and cell cycle phase distribution, suggesting a driver role in cancer progression. ; This work was supported by grant CTQ2017-83810-R (MINECO/FEDER/UE) to F.J.B., SAF2015-65690P to I.P., SAF2017-84092-R and SAF2014-51966-R to R.K., and SAF2017-84934-R to M.V. G.O. acknowledges a Formación de Personal Investigador Fellowship from MINECO (BES-2012-052851). We also thank MINECO for the Severo Ochoa Excellence Accreditation (SEV-2016-0644). |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| تدمد: | 0022-2836 1089-8638 |
| العلاقة: | #PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/CTQ2017-83810-R; CTQ2017-83810-R/AEI/10.13039/501100011033; info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2015-65690-P; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/SAF2017-84092-R; SAF2017-84092-R/AEI/10.13039/501100011033; info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2014-51966-R; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/SAF2017-84934-R; SAF2017-84934-R/AEI/10.13039/501100011033; info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SEV-2016-0644; http://dx.doi.org/10.1016/j.jmb.2019.04.018Test; Sí; Journal of Molecular Biology 431(12): 2298-2319 (2019); http://hdl.handle.net/10261/207622Test; http://dx.doi.org/10.13039/501100003329Test; http://dx.doi.org/10.13039/501100000780Test |
| DOI: | 10.1016/j.jmb.2019.04.018 |
| DOI: | 10.13039/501100003329 |
| DOI: | 10.13039/501100000780 |
| الإتاحة: | https://doi.org/10.1016/j.jmb.2019.04.018Test https://doi.org/10.13039/501100003329Test https://doi.org/10.13039/501100000780Test http://hdl.handle.net/10261/207622Test |
| حقوق: | none |
| رقم الانضمام: | edsbas.DBD25A70 |
| قاعدة البيانات: | BASE |
| تدمد: | 00222836 10898638 |
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| DOI: | 10.1016/j.jmb.2019.04.018 |