Gspt1, also known as G1 to S phase transition 1, is a key translation termination factor [2,4]. It interacts with eRF1 to facilitate the translation termination process, which is crucial for normal protein synthesis and cellular function [4].

Studies have shown that Gspt1 is significantly overexpressed in various cancer tissues and cells, including acute myeloid leukemia, MYC-driven lung cancer, liver cancer, and glioblastoma [2,4,5,6]. Drugs that degrade Gspt1 via the CRL4CRBN ubiquitin ligase are a new class of cancer therapy in active clinical development [3]. For example, CC-885, a cereblon modulator, can recruit Gspt1 to the CRL4(CRBN) ubiquitin ligase, leading to Gspt1's ubiquitination and degradation, which mediates its anti-tumor activity [1]. In acute myeloid leukemia, Gspt1 degradation leads to impaired translation termination, activation of the integrated stress response pathway, and TP53-independent cell death, while sparing normal hematopoietic stem cells [3]. In glioblastoma, depletion of Gspt1 can enhance apoptosis and prolong the survival period of nude mice with transplanted brain tumors [6].

In conclusion, Gspt1 is essential for normal translation termination. Its overexpression in multiple cancers makes it a promising anti-tumor target. Studies using Gspt1-degrading drugs in mouse models have revealed its role in cancer cell death and the sparing of normal hematopoietic stem cells, providing a mechanistic basis for using Gspt1 degraders in cancer treatment, especially for TP53-mutant acute myeloid leukemia [3].