eRF3a/GSPT1

Eukaryotic release factor 3a (eRF3a), also known as G1 to S phase transition protein 1 (GSPT1), is a translation termination factor that forms a functional complex with eukaryotic release factor 1 (eRF1) to promote stop codon recognition and polypeptide release during protein synthesis^[1][2]. GSPT1 belongs to the eRF3 family of GTP-binding proteins and contributes to translation termination through its interaction with eRF1 and regulation of GTP-dependent termination reactions^[1][3]. Mechanistically, GSPT1 contains an N-terminal regulatory region and a C-terminal eRF3 domain that interacts with eRF1 and other translation-associated factors^[2]. In disease-related models, altered GSPT1 expression and activity have been investigated in cancer biology because translation regulation influences tumor cell growth and survival. GSPT1 depletion reduces proliferation and induces apoptosis in several cancer cell models, supporting its role in maintaining cancer-associated cellular programs^[4]. Compared with the related isoform eRF3b/GSPT2, GSPT1 is more broadly expressed and has distinct biological functions despite sharing conserved eRF1-interacting regions^[3][5]. Unlike translation initiation factors that regulate ribosome recruitment, GSPT1 functions primarily during translation termination and ribosome recycling processes^[1][2]. For experimental applications, GSPT1 function is studied using genetic depletion, protein interaction analysis, translation assays, and small-molecule degradation approaches^[4][6]. Targeted degradation compounds such as molecular glue degraders have been developed to investigate GSPT1-dependent cellular effects and therapeutic mechanisms in cancer models^[6].