TRIP13

TRIP13, or thyroid hormone receptor interactor 13, is a gene that encodes an ATPase belonging to the PCH2/TRIP13 subfamily of the AAA+ ATPases. It is conserved across metazoans and plays critical roles in chromosome dynamics during meiosis as well as in the mitotic spindle assembly checkpoint, linking chromosome behavior with cell cycle progression.

In meiosis, TRIP13 remodels HORMA domain–containing proteins such as HORMAD1 and HORMAD2. This remodeling promotes their removal from unsynapsed chromosome axes, enabling proper synapsis and progression through prophase I, and supports accurate homologous recombination. In mammals, TRIP13 is required for fertility, and loss of function leads to meiotic arrest and defective gametogenesis.

In mitosis, TRIP13 operates with the MAD2-binding protein p31comet to silence the spindle assembly checkpoint. It catalyzes the conformational transition of MAD2 from the closed, checkpoint-active form to the open form, facilitating disassembly of the mitotic checkpoint complex and allowing anaphase onset. This activity contributes to timely chromosome segregation and mitotic exit.

Clinical significance attributed to TRIP13 includes altered expression in several cancers, where it is often associated with genomic instability and poorer prognosis. Because of its role in checkpoint control and chromosome dynamics, TRIP13 is studied as a potential biomarker and as a therapeutic target to modulate SAC activity in cancer.

Structure and interactions: TRIP13 is an ATPase that can form hexameric assemblies, using ATP hydrolysis to remodel HORMA domain proteins. It interacts with p31comet, MAD2, and other HORMA-domain proteins involved in meiosis, integrating checkpoint regulation with chromosomal behavior.