The proteasome subunit LMP2/β1i in the female genital system

Protein degradation by the ubiquitin-proteasome system is central to cell homeostasis and survival. Defects in this process are associated with diseases such as cancer and neurodegenerative disorders. The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven α subunits, and the two central rings are each formed by seven β1 subunits. Replacement of LMPY by LMP2/β1i increases the capacity of the immunoproteasome to cleave model peptides after hydrophobic and basic residues. LMP2/β1i mediates the cell survival pathway. Embryo implantation involves the invasion of placental extravillous trophoblast cells (EVTs) into the uterus. Normal human placentas or placentas from hydatidiform mole patients were collected and the expression of LMP2/β1i in different cell types including trophoblastic column (TC), cytotrophoblast cells (CTB) and syncytiotrophoblasts (STBs) was examined under different pathological states by pathological analysis. LMP2/β1i expression in TC of partial hydatidiform mole and complete hydatidiform mole placentas was higher than that in TC of normal human placentas. The overexpression of LMP2/β1i in trophoblast cells of hydatidiform moles may contribute to its highly invasive phenotype. LMP2/β1i-deficient mice reportedly exhibit uterine neoplasms, with a disease prevalence of 36% by 12 months of age. Further experiments with human and mouse uterine tissues clarified the biological significance of LMP2/β1i in malignant myometrium transformation and the cell cycle, which implicated LMP2/β1i as an anti-tumorigenic candidate. In this mini review, we covered recent insights into the molecular and cellular pathways involved in LMP2/β1i-mediated biological functions, with a particular focus on embryo implantation and uterine mesenchymal tumorigenesis.