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Acknowledgements The authors gratefully acknowledge research funding from the National Institutes of Health (R00CA201603, R21EB025270, R21EB026175, R21EB030257, R01EB028143, R01HL153857, R01DK72381, R03EB027984, R37DK39773 and UH3TR002155), the National Science Foundation (CBET-EBMS-1936105), the Brigham Research Institute, the Hofvijverkring Visiting Scientist Program, the Dutch Kidney Foundation (18KVP01), Utrecht Institute for Pharmaceutical Sciences and European Unions Horizon 2020 research and innovation programme WIDESPREAD-05-2018-TWINNING Remodel

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54 The observation that deficiency of Puma (or combined deficiency of Puma and Noxa or Puma and p21) promoted the development of C-myc-driven lymphoma, 107,108 which suggested that p53-mediated apoptosis could exert obvious tumor-suppressive effects