E3 ubiquitin-protein ligase pellino homolog 1 (PELI1) (PELI1)

E3 ubiquitin-protein ligase pellino homolog 1 (PELI1) is a highly conserved enzyme that plays a central role in regulating innate and adaptive immune responses by mediating the ubiquitination of key signaling proteins (UniProt, 2024). It functions as both a scaffold and an E3 ligase, catalyzing the attachment of K48-, K63-, and K11-linked ubiquitin chains to substrates such as IRAK1, RIPK1, and NIK, thereby modulating pathways like NF-kappa-B, MAPK, and mTORC1 (Moynagh, 2014; Zhang & Li, 2022). PELI1 is involved in diverse biological processes, including the inflammatory response, cell death mechanisms like necroptosis, and DNA damage repair via homologous recombination (NCBI, 2024; Park et al., 2022). In clinical contexts, PELI1 is often overexpressed in various malignancies, including lung, breast, and pancreatic cancers, where it promotes tumor progression and chemoresistance (Qi et al., 2023). It also contributes to the pathogenesis of inflammatory disorders such as multiple sclerosis and asthma, as well as autoimmune conditions like systemic lupus erythematosus (Park et al., 2022). Due to its multifaceted roles in disease, PELI1 has become an attractive therapeutic target, with small molecule inhibitors like BBT-401 currently being evaluated in clinical trials for inflammatory bowel disease (Patsnap Synapse, 2024).

Other names

Pellino-1Pellino homolog 1Pellino-related intracellular-signaling moleculeRING-type E3 ubiquitin transferase pellino homolog 1Protein pellino homolog 1

Inhibition of E3 ubiquitin ligase activity to modulate pro-inflammatory and oncogenic signaling pathways.