Thyroid hormone receptor interactor 13 (TRIP13) (TRIP13)

Thyroid hormone receptor interactor 13 (TRIP13) is a member of the AAA+ ATPase family that plays a pivotal role in maintaining genomic stability through its regulation of the spindle assembly checkpoint (SAC) and DNA double-strand break repair (UniProt Q15645). It functions primarily by catalyzing the conformational transition of the SAC protein MAD2 from its active closed form (C-MAD2) to its inactive open form (O-MAD2), thereby facilitating the progression of the cell cycle from metaphase to anaphase (Vader et al., 2011). In many human malignancies, including multiple myeloma and various carcinomas, TRIP13 is significantly overexpressed, which correlates with increased chromosomal instability, treatment resistance, and poor clinical outcomes (Sheng et al., 2018). Therapeutic strategies targeting TRIP13 include small molecule inhibitors like DCZ0415, which binds to the ATPase domain, and RNA-based modalities such as siRNA or antisense oligonucleotides designed to reduce TRIP13 mRNA levels (Ji et al., 2020). By inhibiting TRIP13, these agents aim to disrupt the cell cycle and sensitize cancer cells to DNA-damaging therapies, making it a promising target for precision oncology (Wang et al., 2020). High levels of TRIP13 mRNA serve as a potential biomarker for patient stratification and prognosis in clinical settings.

Other names

PCH21-TRIP13Thyroid receptor-interacting protein 13AAA+ ATPase TRIP13Human papillomavirus type 16 E1 protein-binding protein

Inhibition of ATPase activity to prevent the conformational change of MAD2 from C-MAD2 to O-MAD2, thereby maintaining the spindle assembly checkpoint and inducing cell cycle arrest; or degradation of mRNA transcripts via RNA interference to prevent protein synthesis (Vader et al., 2011; Ji et al., 2020).