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PIKK, phosphatidylinositol-3-kinase-related kinase

AlphaFold3-predicted 3D structural modeling suggested that KW substitutions alter both the binding affinity and interaction pattern between HMGB1/2 and Importin Alpha 5 (IMA5, a key nuclear import mediator for HMGB1/2) (Figure S5A-B)

Following hyperosmotic stress, some ribosomal proteins that failed to properly fold can undergo ubiquitination, and RAD23B, a shuttle factor that has ubiquitin-associated domains, further drives LLPS of ubiquitinated ribosomal proteins and nuclear proteasomes, leading to proteasomal removal of misfolded ribosomal proteins

Aging, chronic stress, environmental exposure, poor sleep, and illness can all deplete levels over time, says Patel