Uncovering The Nuclear Pipn-p53 Signalosome In Cancer Cell Migration

In this review, nan authors coming caller findings that uncover a antecedently unappreciated atomic signaling hub: nan PIPn-p53 signalosome. This analyzable not only modulates AKT activation wrong nan nucleus but besides integrates 2 awesome oncogenic pathways-p53 dysregulation and PI3K-AKT amplification-into a unified system driving crab compartment migration and invasion.

Key points of the reappraisal include:

1. Nuclear PIPn signaling expands beyond classical models: Phosphoinositides, agelong thought to beryllium confined to plasma and endomembranes for cytoplasmic signaling, are now shown to shape progressive signaling complexes successful nan nucleus, reshaping our knowing of lipid-mediated regulation.
2. Wild-type and mutant p53 service arsenic atomic scaffolds: Both forms of p53 anchor atomic PIPns and facilitate nan assembly of lipid-protein complexes (signalosomes), straight influencing cistron expression, chromatin remodeling, and cytoskeletal dynamics.
3. De novo AKT activation successful nan nucleus: Unlike canonical membrane-bound activation, atomic AKT is activated by PtdIns(3,4,5)P₃ generated by nan PIPn-p53 complex. This activation promotes crab compartment endurance and migration-particularly nether stress.
4. Therapeutic implications: Disruption of nan atomic PIPn-p53 signalosome, particularly successful mutant p53-driven cancers, could impair metastasis. Targeting nuclear-specific PIPn enzymes aliases restoring p53 usability whitethorn synergize pinch PI3K/AKT inhibitors to suppress crab dissemination.

This reappraisal highlights nan atomic PIPn-p53 signalosome arsenic a cardinal regulator of crab compartment motility and a promising target for metastasis therapy. The activity entitled "The Nuclear Phosphoinositide-p53 Signalosome successful nan Regulation of Cell Motility" was published successful Protein & Cell (Advance entree May 26, 2025).