bims-hypusi Biomed News
on Hypusine and eIF5A
Issue of 2026–06–21
two papers selected by
Sebastian J. Hofer, Max Delbrück Center
  1. Regulation of EIF5A and hypusination by p53 determines colorectal cancer cell fitness.
  2. Blood DNA methylation of EIF5A and TGIF1 is associated with adipose tissue health and metabolic outcomes in obesity: a multi-cohort study.
  1. Cancer Lett. 2026 Jun 15. pii: S0304-3835(26)00446-5. [Epub ahead of print]656 218682
    Regulation of EIF5A and hypusination by p53 determines colorectal cancer cell fitness.
    Alain P Gobert, Caroline V Hawkins, Mohammad Asim, Daniel P Barry, Alberto G Delgado, Regina N Tyree, Kate S Carson, Nikhil P S Kahlon, Mark V Ciampa, Kristie L Rose, Purvi Patel, Ganesh V Pusapati, Rajat Rohatgi, Wang Yu, Shilin Zhao, Lori A Coburn, M Blanca Piazuelo, Keith T Wilson.
      Hypusination of eukaryotic translation initiation factor 5 A (EIF5A) by the enzyme deoxyhypusine synthase (DHPS) is a mechanism of regulation of translation that plays a role in cell proliferation. Herein, we assessed the role of hypusination in established colorectal cancer (CRC). Using molecular and biochemical approaches in established CRC cell lines and human colon organoids, we found that the tumor suppressor p53 is a critical regulator of expression of the gene EIF5A1 in the colon, thus supporting EIF5A synthesis and hypusination. Therefore, tissues and cells isolated from patients with CRC harboring TP53 mutation associated with loss of function of p53 exhibited a marked reduction of EIF5A and hypusine level. Further, TP53 mutant CRC cells remained unresponsive to a DHPS inhibitor. However, restoration of wild-type TP53 in these mutated cells supported hypusination-dependent translation of proteins involved in cell growth and rendered them susceptible to DHPS inhibition. Our studies show that loss of EIF5A is an unrecognized molecular feature of TP53 mutation in CRC cells and patients with WT TP53 CRC may benefit from drugs that can inhibit hypusination.
    Keywords:  Colon; Colorectal cancer; Deoxyhypusine synthase; Hypusine; Polyamine; Tumor suppressor p53
    DOI:  https://doi.org/10.1016/j.canlet.2026.218682
  2. Clin Epigenetics. 2026 Jun 16. pii: 118. [Epub ahead of print]18(1):
    Blood DNA methylation of EIF5A and TGIF1 is associated with adipose tissue health and metabolic outcomes in obesity: a multi-cohort study.
    Sophie Ruf, Anne Hoffmann, Luise Müller, Kathrin Landgraf, Mandy Vogel, Emil Jørsboe, Phil Kubitz, Arne Dietrich, Adhideb Ghosh, Falko Noé, Christian Wolfrum, Melina Claussnitzer, Hans Hauner, Michael Stumvoll, Ronny Baber, Matthias Blüher, Antje Körner, Peter Kovacs, Maria Keller.
       BACKGROUND: Blood-based DNA methylation has been linked to obesity and metabolic health, yet its relationship to adipose tissue function remains incompletely understood. This study aimed to investigate the epigenetic regulation of EIF5A (Eukaryotic translation initiation factor 5A-1) and TGIF1 (TGFB Induced Factor Homeobox 1) across blood and adipose tissue in obesity.
    METHODS: Candidate genes were identified using a multi-step gene selection approach integrating transcriptomic and epigenomic data from blood and adipose tissue samples obtained from children and adults across four diverse population- and disease-focused cohorts. Genes were prioritized based on differential DNA methylation and gene expression in obesity. Targeted bisulfite sequencing of EIF5A and TGIF1 was conducted in blood samples from adults across BMI-defined groups and from children prior to the development of obesity, to validate candidate loci and to examine associations with metabolic and adipocyte-related phenotypes.
    RESULTS: In adults from the Leipzig Obesity BioBank, blood DNA methylation (N = 150) of both EIF5A and TGIF1 was significantly increased in individuals with obesity. EIF5A mRNA expression (N = 1554) was significantly higher in omental-visceral adipose tissue compared with subcutaneous adipose tissue. Blood DNA methylation of EIF5A was associated with body mass index (BMI), glycated hemoglobin (HbA1c), and leukocyte counts, particularly among individuals with type 2 diabetes mellitus. In children, blood DNA methylation (N = 75) of EIF5A was associated with longitudinal HbA1c trajectories. For TGIF1, DNA methylation levels were increased in subcutaneous adipose tissue (N = 219) of children with obesity and correlated with fasting serum insulin concentrations. Across cohorts, TGIF1 regulation in both blood and adipose tissue showed consistent associations with adipocyte size. Notably, blood DNA methylation of TGIF1 in childhood was associated with body fat mass and HbA1c at later follow-up despite normal weight at baseline.
    CONCLUSION: EIF5A and TGIF1 DNA methylation represent cross-tissue epigenetic signatures linking blood-based DNA methylation to adipose tissue dysfunction, adipocyte hypertrophy, and early metabolic risk. These findings support the potential of blood DNA methylation markers to reflect adipose tissue health and metabolic outcomes across the lifespan.
    Keywords:  Adipose tissue; Blood; Childhood; DNA methylation; Epigenetics; Metabolism; Obesity; mRNA expression
    DOI:  https://doi.org/10.1186/s13148-026-02177-y
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