G1 to S phase transition protein 1 homolog (GSPT1)

G1 to S phase transition protein 1 homolog (GSPT1), also known as eRF3a, is a GTPase that plays a fundamental role in eukaryotic protein translation termination. It forms a complex with eRF1 to recognize stop codons and facilitate the release of nascent polypeptide chains from the ribosome (UniProt P15170). Beyond translation, GSPT1 is involved in regulating the transition of cells from the G1 to the S phase of the cell cycle and contributes to the control of mRNA stability. In recent years, GSPT1 has gained significant attention as a therapeutic target in oncology, particularly for acute myeloid leukemia (AML), due to its susceptibility to targeted protein degradation. Molecular glue degraders, such as CC-90009, recruit GSPT1 to the CRL4-CRBN E3 ubiquitin ligase complex, leading to its polyubiquitination and subsequent proteasomal degradation, which triggers rapid apoptosis in MYC-driven cancer cells (Surka et al., 2021, Nature Communications).

Other names

eRF3aEukaryotic peptide chain release factor GTP-binding subunit 3aG1 to S phase transition 1GST1

Targeted protein degradation via molecular glue recruitment to the CRL4-CRBN E3 ubiquitin ligase complex.