G1 to S phase transition 1 (GSPT1) (GSPT1)

G1 to S phase transition 1 (GSPT1), also known as eRF3a, is a GTPase that plays a critical role in eukaryotic translation termination by facilitating the release of nascent polypeptide chains from the ribosome (UniProt P15170). In the context of oncology, GSPT1 has emerged as a high-priority therapeutic target, particularly in acute myeloid leukemia (AML), where its overexpression is linked to poor clinical outcomes (Surka et al., 2021). Therapeutic strategies involve the use of molecular glue degraders, such as CC-90009, which reprogram the Cereblon (CRBN) E3 ubiquitin ligase complex to recognize GSPT1 as a neosubstrate (Hansen et al., 2021). This recruitment leads to the polyubiquitination and subsequent proteasomal degradation of GSPT1, triggering rapid apoptosis in cancer cells that are highly dependent on protein synthesis (Matyskiela et al., 2016). Because GSPT1 is essential for cell viability, its targeted depletion provides a potent mechanism to bypass traditional inhibitory pathways. However, clinical application requires careful management of hematologic toxicities, such as neutropenia, due to the protein's role in normal hematopoietic stem cell function (Lopez-Girona et al., 2020).

Other names

eRF3aeukaryotic peptide chain release factor GTP-binding subunit ERF3AG1 to S phase transition protein 1

Molecular glue-induced targeted protein degradation via the CRL4-CRBN E3 ubiquitin ligase complex