% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Minen:300775,
      author       = {R. I. Minen$^*$ and M. D. Camalle and T. J. Schwertfeger
                      and F. Abdulhakim and H. Reish and L. Perez de Souza and J.
                      C. Moreno and A. Schilmiller and V. P. Thirumalaikumar and
                      P. Agarwal and C. F. Plecki and A. R. Fernie and H. Hirt and
                      F. C. Schroeder and A. Skirycz},
      title        = {{C}haracterization of the cyclic dipeptide
                      cyclo({H}is-{P}ro) in {A}rabidopsis.},
      journal      = {Plant physiology},
      volume       = {198},
      number       = {1},
      issn         = {0032-0889},
      address      = {Oxford},
      publisher    = {Oxford University Press},
      reportid     = {DKFZ-2025-00923},
      pages        = {kiaf174},
      year         = {2025},
      note         = {#EA:A050# / 2025 Apr 30;198(1):kiaf174},
      abstract     = {Diketopiperazines (DKPs) are chemically and functionally
                      diverse cyclic dipeptides associated primarily with
                      microbes. Few DKPs have been reported from plants and
                      animals; the best characterized is cyclo(His-Pro), found in
                      the mammalian central nervous system, where it arises from
                      the proteolytic cleavage of a thyrotropin-releasing
                      tripeptide hormone. Herein, we report the identification of
                      cyclo(His-Pro) in Arabidopsis (Arabidopsis thaliana), where
                      its levels increase upon abiotic stress conditions,
                      including high salt, heat, and cold. To screen for potential
                      protein targets, we used isothermal shift assays (iTSA),
                      which examine changes in protein melting stability upon
                      ligand binding. Among the identified proteins, we focused on
                      the glycolytic enzyme, cytosolic glyceraldehyde-3-phosphate
                      dehydrogenase (GAPC1). Binding between the GAPC1 protein and
                      cyclo(His-Pro) was validated using nano differential
                      scanning fluorimetry (nanoDSF) and microscale thermophoresis
                      (MST), and we could further demonstrate that cyclo(His-Pro)
                      inhibits GAPC1 activity with an IC50 of approximately 200
                      μM. This inhibition was conserved in human GAPDH.
                      Inhibition of glyceraldehyde-3-phosphate dehydrogenase
                      activity has previously been reported to reroute carbon from
                      glycolysis towards the pentose phosphate pathway.
                      Accordingly, cyclo(His-Pro) supplementation augmented NADPH
                      levels, increasing the NADPH/NADP+ ratio. Phenotypic
                      screening revealed that plants supplemented with
                      cyclo(His-Pro) were more tolerant to high salt stress, as
                      manifested by higher biomass, which we show is dependent on
                      GAPC1/2. Our work reports the identification and functional
                      characterization of cyclo(His-Pro) as a modulator of
                      glyceraldehyde-3-phosphate dehydrogenase in plants.},
      cin          = {A050},
      ddc          = {580},
      cid          = {I:(DE-He78)A050-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40317191},
      doi          = {10.1093/plphys/kiaf174},
      url          = {https://inrepo02.dkfz.de/record/300775},
}