Phosphatidylethanolamine-binding protein 4 (PEBP4)

Phosphatidylethanolamine-binding protein 4 (PEBP4) is a secreted, glycosylated scaffold protein belonging to the PEBP family, which includes several conserved members across species. Unlike most other PEBP family members, PEBP4 is secreted due to its N-terminal signal peptide and C-terminal domain; it is involved in diverse signal transduction pathways. PEBP4 modulates Akt activation, and depending on context and expression levels, may inhibit or promote ERK/JNK pathway activity. PEBP4 promotes tumorigenesis and progression in various cancers, conferring resistance to therapy, and acts as a negative regulator of liver fibrosis by suppressing NF-κB signaling. Its expression correlates with disease severity in cancer and potentially with fibrosis outcomes. While experimental inhibitors (e.g., siRNA, shRNA) and pathway inhibitors (e.g., PDTC) modulate its activity in research settings, no approved drugs currently target PEBP4. Potential therapeutic targeting faces challenges due to the protein's involvement in multiple key survival and differentiation pathways and lack of specificity for disease states[1][2].

Other names

PEBP4CORK1Phosphatidylethanolamine-binding protein 4hPEBP4Protein cousin-of-RKIP 1Epididymis secretory protein Li 300Epididymis secretory sperm binding proteinHEL-S-300PRO4408MGC22776GWTM1933cousin-of-RKIP 1 proteinCORK-1UNQ1933/PRO4408

Inhibition or reduction of PEBP4 (e.g., by siRNA/shRNA) increases apoptosis and reduces invasiveness in cancer cells via suppression of Akt signaling and other survival/proliferation pathways. NF-κB inhibitors may reverse enhanced fibrosis caused by PEBP4 deficiency through blocking NF-κB pathway activation. Experimental data suggest modulation of PI3K/Akt/mTOR, ERK/JNK, and Sonic Hedgehog pathways, but this is context- and disease-specific.