خريطة
p38γ is essential for cell cycle progression and liver tumorigenesis
| العنوان: | p38γ is essential for cell cycle progression and liver tumorigenesis |
|---|---|
| المؤلفون: | Tomás-Loba, Antonia, Manieri, Elisa, González-Terán, Bárbara, Mora, Alfonso, Leiva-Vega, Luis, Santamans, Ayelén M., Romero-Becerra, Rafael, Rodríguez, Elena, Pintor-Chocano, Aránzazu, Feixas, Ferran, López, Juan Antonio, Caballero, Beatriz, Trakala, Marianna, Blanco, Óscar, Torres, Jorge L., Hernández-Cosido, Lourdes, Montalvo-Romeral, Valle, Matesanz, Nuria, Roche-Molina, Marta, Bernal, Juan Antonio, Mischo, Hannah, León, Marta, Caballero, Ainoa, Miranda-Saavedra, Diego, Ruiz-Cabello, Jesús, Nevzorova, Yulia A., Cubero, Francisco Javier, Bravo, Jerónimo, Vázquez, Jesús, Malumbres, Marcos, Marcos, Miguel, Osuna, Sílvia, Sabio, Guadalupe |
| المساهمون: | Ministerio de Ciencia, Innovación y Universidades (España), Fundación "la Caixa", Fundación Ramón Areces, European Research Council, Lilly Deutschland, Fundación BBVA, Comunidad de Madrid, German Research Foundation |
| بيانات النشر: | Nature Publishing Group |
| سنة النشر: | 2019 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| الوصف: | 27 páginas, 4 figuras. Contiene material suplementario, método, 6 figuras en: https://doi.org/10.1038/s41586-019-1112-8Test ; The cell cycle is a tightly regulated process that is controlled by the conserved cyclin-dependent kinase (CDK)-cyclin protein complex1. However, control of the G0-to-G1 transition is not completely understood. Here we demonstrate that p38 MAPK gamma (p38γ) acts as a CDK-like kinase and thus cooperates with CDKs, regulating entry into the cell cycle. p38γ shares high sequence homology, inhibition sensitivity and substrate specificity with CDK family members. In mouse hepatocytes, p38γ induces proliferation after partial hepatectomy by promoting the phosphorylation of retinoblastoma tumour suppressor protein at known CDK target residues. Lack of p38γ or treatment with the p38γ inhibitor pirfenidone protects against the chemically induced formation of liver tumours. Furthermore, biopsies of human hepatocellular carcinoma show high expression of p38γ, suggesting that p38γ could be a therapeutic target in the treatment of this disease ; s We thank S. Bartlett for English editing, D. Engelberg for the constitutively active mutants, the Division of Signal Transduction Therapy for recombinant proteins, and CNIC Advanced Imaging and Vector Units for technical support. G.S. (RYC-2009-04972), F.J.C. (RYC-2014-15242), and Y.A.N. (RYC-2015-17438) are investigators of the Ramón y Cajal Program. E.M. and M.T. were awarded La Caixa fellowships and R.R.-B. was a fellow of the Fundación Ramón Areces-UAM and FPU. B.G.-T. is a fellow of the FPI Severo Ochoa CNIC program (SVP-2013-067639). F.J.C. is a Gilead Liver Research Scholar. This work was funded by grants supported in part by funds from the European Regional Development Fund: the European Union’s Seventh Framework Programme (FP7/2007-2013) ERC 260464, EFSD/Lilly European Diabetes Research Programme Dr Sabio, 2017 Leonardo Grant for Researchers and Cultural Creators, BBVA Foundation (InvestigadoresBBVA-2017) IN[17]_BBM_BAS_0066, MINECO-FEDER ... |
| نوع الوثيقة: | map |
| اللغة: | English |
| تدمد: | 0028-0836 1476-4687 |
| العلاقة: | #PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2015-67077-R; info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2017-89901-R; info:eu-repo/grantAgreement/EC/FP7/260464; info:eu-repo/grantAgreement/EC/H2020/679001; http://dx.doi.org/10.1038/s41586-019-1112-8Test; Sí; Nature 568(7753):557-560 (2019); http://hdl.handle.net/10261/194840Test; http://dx.doi.org/10.13039/100008054Test; http://dx.doi.org/10.13039/501100001659Test; http://dx.doi.org/10.13039/100012818Test; http://dx.doi.org/10.13039/100007406Test; http://dx.doi.org/10.13039/100006676Test; http://dx.doi.org/10.13039/501100000781Test |
| DOI: | 10.1038/s41586-019-1112-8 |
| DOI: | 10.13039/100008054 |
| DOI: | 10.13039/501100001659 |
| DOI: | 10.13039/100012818 |
| DOI: | 10.13039/100007406 |
| DOI: | 10.13039/100006676 |
| DOI: | 10.13039/501100000781 |
| الإتاحة: | https://doi.org/10.1038/s41586-019-1112-8Test https://doi.org/10.13039/100008054Test https://doi.org/10.13039/501100001659Test https://doi.org/10.13039/100012818Test https://doi.org/10.13039/100007406Test https://doi.org/10.13039/100006676Test https://doi.org/10.13039/501100000781Test http://hdl.handle.net/10261/194840Test |
| حقوق: | none |
| رقم الانضمام: | edsbas.F0290EE1 |
| قاعدة البيانات: | BASE |
| تدمد: | 00280836 14764687 |
|---|---|
| DOI: | 10.1038/s41586-019-1112-8 |