GNPTAB-STING Interaction Interface

Pro-senescent independent of enzymatic activity

A noncanonical STING activation pathway where direct binding of GNPTAB to STING triggers innate immune signaling and cellular senescence, offering a new target for mitigating age-related dysfunction.

Yin, Jian · Gao, Yizhou · Jiang, Xiaoyu · Cai, Yusheng · Li, Heng · Cao, Tianling · Wang, Min · He, Yifang · Hongkai, Zhao · Zhang, Sheng · Ma, Shuai · Wang, Si · Liu, Guanghui · Zhang, Weiqi · Qu, Jing

Protein and Cell 2026

Advantages

Acts independently of enzymatic activity

GNPTAB's pro-senescent function occurs independently of its canonical enzymatic role; instead, it binds STING directly.

Single interface drives senescence

GNPTAB binds STING via a specific interface (E1119); the E1119A mutant preserves lysosomal function but fails to induce senescence.

STING depletion blocks effect

STING depletion abolishes GNPTAB-driven senescence, confirming pathway dependence on STING.

Druggable senescence target

This interface is nominated as a potential target for mitigating age-related cellular dysfunction.

Applications