PDCL3 Human

PhLP3 forms a ternary complex with the ATP-dependent molecular chaperone CCT (chaperonin containing TCP-1) and its folding client tubulin . In vitro studies suggest that PhLP3 plays an inhibitory role in β-tubulin folding, while in vivo genetic studies indicate that PhLP3 is required for the correct folding of β-tubulin . This dual role highlights the complexity of PhLP3’s function in cellular processes.

PhLP3 has been shown to promote cytoskeletal remodeling in a MAPK (mitogen-activated protein kinase) and RhoA-dependent manner . Overexpression of PhLP3 in mammalian cells can lead to an imbalance of α and β tubulin subunits, microtubule disassembly, and cell death . Conversely, RNA silencing of PhLP3 increases RhoA-dependent actin filament formation and focal adhesion formation, promoting a dramatic elongated fibroblast-like change in cell morphology . This suggests that PhLP3 levels are finely balanced in mammalian cells and play a crucial role in maintaining cytoskeletal integrity.

PhLP3 has also been identified as a novel chaperone protein involved in the generation of functional VEGF (vascular endothelial growth factor) receptor 2 (VEGFR-2) . Angiogenesis, the formation of new blood vessels, is primarily driven by the VEGF-induced activation of VEGFR-2. PhLP3 binds to the juxtamembrane domain of VEGFR-2 and controls its abundance by inhibiting ubiquitination and degradation . This regulation is essential for VEGFR-2-dependent endothelial capillary tube formation and proliferation, making PhLP3 a critical player in angiogenesis and a potential therapeutic target for blocking tumor growth and ocular neovascularization .