Prune exopolyphosphatase 1 (PRUNE1)

Prune exopolyphosphatase 1 (PRUNE1) is an enzyme and member of the DHH phosphoesterase superfamily with both exopolyphosphatase and phosphodiesterase activities. Its N-terminal DHH domain hydrolyzes short-chain polyphosphates, and it also acts on the cyclic nucleotides cAMP and cGMP. Highly expressed during fetal neurodevelopment and in various cancers, PRUNE1 regulates cell proliferation, migration, and cytoskeletal organization via interactions with key signaling modulators including GSK-3β and Nm23-H1, influencing pathways such as Wnt and TGF-β, as well as processes like EMT. Pathogenic mutations cause a recessive neurodevelopmental disorder (NMIHBA), while overexpression is linked to tumor progression and metastasis. PRUNE1 is being explored as a therapeutic target for both cancer (inhibition) and rare neurodevelopmental diseases (functional rescue or modulation), but its pleiotropic roles pose development and safety challenges.

Other names

PRUNEDRES-17DRES17hPruneHTCD37H-PRUNEDrosophila-related expressed sequence 17protein prune homolog 1NMIHBAexopolyphosphatase PRUNE1

Inhibition of PRUNE1 phosphodiesterase or exopolyphosphatase activity to suppress cell migration and metastasis (e.g., by AA7.1 or dipyridamole); Disruption of PRUNE1–protein interactions (e.g., inhibition of signaling partnerships, such as with GSK-3β or Nm23-H1)