Phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3) (PIK3C3)

Class III Phosphoinositide 3-kinase (PI3K), primarily known by its catalytic subunit VPS34 (PIK3C3), is a lipid kinase that specifically phosphorylates phosphatidylinositol to generate phosphatidylinositol 3-phosphate (PtdIns3P). This signaling lipid is a fundamental regulator of intracellular membrane trafficking, playing a central role in the initiation of autophagy, endosome maturation, and phagocytosis [UniProt: Q8NEB9]. By recruiting effector proteins that recognize PtdIns3P, VPS34 facilitates the formation of autophagosomes and the sorting of cargo within the endolysosomal system. In oncology, VPS34 is frequently exploited by tumor cells to survive metabolic stress and evade immune surveillance, making it a significant target for small-molecule inhibitors like SAR405 [PubMed: 24679539]. Conversely, its dysfunction is implicated in neurodegenerative diseases where the failure of autophagic clearance leads to the accumulation of toxic protein aggregates. Therapeutic development currently focuses on selective VPS34 inhibitors to sensitize tumors to chemotherapy and modulate the tumor microenvironment.

Other names

VPS34Class III phosphoinositide 3-kinasehVps34Phosphoinositide-3-kinase class 3Vacuolar protein sorting-associated protein 34

Inhibition of the catalytic activity of VPS34 prevents the phosphorylation of phosphatidylinositol to phosphatidylinositol 3-phosphate (PtdIns3P), thereby blocking the recruitment of FYVE and PX domain-containing proteins essential for autophagosome formation and endosomal maturation [PubMed: 24679539, 25130555].