Golgi-associated plant pathogenesis-related protein 1 (GAPR-1) (GAPR-1)

Golgi-associated plant pathogenesis-related protein 1 (GAPR-1), also known as GLIPR2, is a mammalian protein belonging to the CAP superfamily that primarily localizes to the cytosolic leaflet of the Golgi membrane [5, 10, 11]. It functions as a negative regulator of autophagy by sequestering Beclin 1, a key initiator of the autophagic process, at the Golgi apparatus [7, 8, 11]. Beyond its role in autophagy, GAPR-1 is involved in innate immune signaling, where it enhances type I interferon responses via the TLR4 pathway [2, 11]. It also possesses unique amyloidogenic properties, forming fibrils that can inhibit the aggregation of other proteins such as Amyloid-beta [1, 6, 11]. GAPR-1 is implicated in several diseases, including various cancers, neurodegenerative disorders like multiple sclerosis, and fibrotic conditions such as kidney and liver fibrosis [3, 6, 8, 9, 11]. Due to its inhibitory effect on autophagy, it has become a therapeutic target for conditions characterized by autophagic dysfunction [13, 17, 18]. The synthetic peptide Tat-Beclin 1 targets GAPR-1 to release Beclin 1 and induce autophagy, showing potential for treating Huntington's disease and metabolic liver disorders [7, 17, 18].

Other names

GLIPR2Glioma pathogenesis-related protein 2C9orf19Golgi-associated PR-1 protein

Tat-Beclin 1 peptide binds to GAPR-1, preventing it from sequestering Beclin 1 at the Golgi membrane, which releases Beclin 1 to initiate autophagy.