SIRT7 and p53 interaction in embryonic development and tumorigenesis
Vazquez Prat, Berta Nieves (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Fernández-Duran, Irene (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Hernandez, Yurdiana (Rutgers University (Piscataway, Estats Units d'Amèrica))
Tarighi, Shahriar (Max-Planck-Institute for Heart and Lung Research. Department of Cardiac Development and Remodeling)
Thackray, Joshua K. (Rutgers University (Piscataway, Estats Units d'Amèrica))
Espinosa-Alcantud, María Dolores (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Kumari, Poonam (Max-Planck-Institute for Heart and Lung Research. Department of Cardiac Development and Remodeling)
Ianni, Alessandro (Max-Planck-Institute for Heart and Lung Research. Department of Cardiac Development and Remodeling)
Cesaire, Lionel (The City University of New York. Department of Science)
Braun, Thomas (Max-Planck-Institute for Heart and Lung Research. Department of Cardiac Development and Remodeling)
Esteller, M (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Tischfield, Jay (Rutgers University (Piscataway, Estats Units d'Amèrica))
Vaquero, Alejandro (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Serrano, Lourdes (The City University of New York. Department of Science)

Fecha:	2024
Resumen:	p53 is a hallmark tumor suppressor due in part to its role in cell cycle progression, DNA damage repair, and cellular apoptosis; its protein activity interrelates with the Sirtuin family of proteins, major regulators of the cellular response to metabolic, oxidative, and genotoxic stress. In the recent years, mammalian Sirtuin 7 (SIRT7) has emerged as a pivotal regulator of p53, fine-tuning its activity in a context dependent manner. SIRT7 is frequently overexpressed in human cancer, yet its precise role in tumorigenesis and whether it involves p53 regulation is insufficiently understood. Depletion of SIRT7 in mice results in impaired embryo development and premature aging. While p53 activity has been suggested to contribute to tissue specific dysfunction in adult Sirt7 -/- mice, whether this also applies during development is currently unknown. By generating SIRT7 and p53 double-knockout mice, here we show that the demise of SIRT7-deficient embryos is not the result of p53 activity. Notably, although SIRT7 is commonly considered an oncogene, SIRT7 haploinsufficiency increases tumorigenesis in p53 knockout mice. Remarkably, in specific human tumors harboring p53 mutation, we identified that SIRT7 low expression correlates with poor patient prognosis. Transcriptomic analysis unveils a previously unrecognized interplay between SIRT7 and p53 in epithelial-to-mesenchymal transition (EMT) and extracellular matrix regulation with major implications for our understanding of embryonic development and tumor progression.
Ayudas:	Agencia Estatal de Investigación PID2020-117284RB-I00
Nota:	The authors declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by internal funds from the Human Genetics Institute of New Jersey (HGINJ) and by CRISP (to LS), the Worldwide Cancer Research (to AV; grant # 18-0404), the Spanish Ministry of Economy and Competitiveness (MINECO) (to AV; grant #PID 2020-117284RB-I00), and cofounded by FEDER funds/European Regional Development Fun (ERDF)-A Way to Build Europe (to AV); BV was funded by the European Commission's Horizon 2020 research and innovation programme (Marie S\u0142odowska-Curie grant #895979) and by the Agency for Management of University and Research Grants (Beatriu de Pinos fellowship # 2016 BP 00250). AI was funded by the European Commission's Horizon 2021 (Marie Sk\u0142odowska-Curie grant #101065013) and the Deutsche Forschungsgemeinschaft (DFG IA 94/1-1).
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	P53 ; SIRTUIN ; Sirt7 ; Embryonic development ; Tumor suppressor ; Gene expression ; Epithelial to mesenchymal transition
Publicado en:	Frontiers in Cell and Developmental Biology, Vol. 11 (january 2024) , ISSN 2296-634X

DOI: 10.3389/fcell.2023.1281730
PMID: 38234684

14 p, 3.2 MB

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