Inositol (1,4,5)-trisphosphate 5-phosphatase promotes survival of uveal melanoma by regulating oncogenic G protein-driven calcium oscillations.

ABSTRACT: Mutant constitutively active (CA) G protein α-subunits encoded by GNAQ or GNA11 (CA-GNAQ/11) drive uveal melanoma (UM), occur in uncommon subtypes of other cancers, and cause Sturge-Weber syndrome and other capillary malformations. CA-GNAQ/11 activates phospholipase Cβ, which cleaves phosphatidylinositol (4,5)-bisphosphate at high rate to produce diacylglycerol that drives oncogenesis and inositol (1,4,5)-trisphosphate (IP3) that releases Ca²⁺ from intracellular stores and triggers store-operated Ca²⁺ entry. For poorly understood reasons, high IP3 flux in UM cells does not elicit Ca²⁺ overload and death. To address this question, we studied INPP5A, a farnesylated, membrane-bound inositol polyphosphate 5-phosphatase that degrades IP3. We showed that INPP5A i

SUBMITTER: Onken MD 

PROVIDER: S-EPMC12450637 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature