SIRT7 and p53 interaction in embryonic development and tumorigenesis
Por:
Vazquez, BN, Fernandez-Duran, I, Hernandez, Y, Tarighi, S, Thackray, JK, Espinosa-Alcantud, M, Kumari, P, Ianni, A, Cesaire, L, Braun, T, Esteller, M, Tischfield, J, Vaquero, A and Serrano, L
Publicada:
3 ene 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.
Filiaciones:
:
Josep Carreras Leukaemia Res Inst IJC, Chromatin Biol Lab, Badalona, Spain
Univ Autonoma Barcelona UAB, Dept Biol Cellular Fisiol & Immunol, Unitat Citol & Histol, Cerdanyola Del Valles, Barcelona, Spain
:
Josep Carreras Leukaemia Res Inst IJC, Chromatin Biol Lab, Badalona, Spain
Hernandez, Y:
Rutgers State Univ, Human Genet Inst New Jersey HGINJ, Dept Genet, Piscataway, NJ USA
Tarighi, S:
Max Planck Inst Heart & Lung Res, Dept Cardiac Dev & Remodeling, Bad Nauheim, Germany
Thackray, JK:
Rutgers State Univ, Human Genet Inst New Jersey HGINJ, Dept Genet, Piscataway, NJ USA
:
Josep Carreras Leukaemia Res Inst IJC, Chromatin Biol Lab, Badalona, Spain
Kumari, P:
Max Planck Inst Heart & Lung Res, Dept Cardiac Dev & Remodeling, Bad Nauheim, Germany
Ianni, A:
Josep Carreras Leukaemia Res Inst IJC, Chromatin Biol Lab, Badalona, Spain
Max Planck Inst Heart & Lung Res, Dept Cardiac Dev & Remodeling, Bad Nauheim, Germany
Cesaire, L:
City Univ New York CUNY, Borough Manhattan Community Coll BMCC, Dept Sci, New York, NY 10007 USA
Braun, T:
Max Planck Inst Heart & Lung Res, Dept Cardiac Dev & Remodeling, Bad Nauheim, Germany
:
Josep Carreras Leukaemia Res Inst IJC, Canc Epigenet Grp, Barcelona, Spain
Ctr Invest Biomed Red Canc CIBERONC, Madrid, Spain
Inst Catalana Recerca & Estudis Avancats ICREA, Barcelona, Catalonia, Spain
Univ Barcelona UB, Sch Med & Hlth Sci, Dept Physiol Sci, Barcelona, Catalonia, Spain
Tischfield, J:
Rutgers State Univ, Human Genet Inst New Jersey HGINJ, Dept Genet, Piscataway, NJ USA
:
Josep Carreras Leukaemia Res Inst IJC, Chromatin Biol Lab, Badalona, Spain
Serrano, L:
City Univ New York CUNY, Borough Manhattan Community Coll BMCC, Dept Sci, New York, NY 10007 USA
gold, Green Published
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