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In ruminant, adequate endometrial function is a major factor affecting implantation and economic efficiency. However, the precise mechanisms regulating goat endometrial function during the peri-implantation period of pregnancy are still unclear. Here, we investigated the functional role and signal transduction of the fifth component of the constitutive photomorphogenic-9 signalosome (COPS5) in the regulation of endometrial function in endometrial epithelial cells (EECs). Our results showed that hormones decreased COPS5 expression, and COPS5-mediated regulation of endometrial function. We also found that knockdown of COPS5 hindered EECs proliferation by the G1-phase cell cycle arrest. Hormones affected the activity of COPS5 through hormones receptors, while feedback from the expression of COPS5 regulated the transcription of the receptor. Moreover, knockdown of endoplasmic reticulum (ER) to nucleus signaling 1 (ERN1) via si-ERN1 partly inhibited endometrial function in shCOPS5 EECs. In addition, blocking the mTOR pathway by rapamycin promoted endometrial function in si-ERN1-transfected shCOPS5 EECs. Overall, these results suggest that COPS5 negatively regulates goat endometrial function via the ERN1 and mTOR-autophagy pathways and provide new insights into the mechanistic pathways of COPS5 during female reproductive development.
This article was published in the following journal.
Name: Journal of cellular physiology
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An adaptor protein component of the MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1 that forms stoichiometric complexes with TOR KINASES, which it negatively regulates. It functions as a positive regulator of RIBOSOMAL PROTEIN S6 KINASES.
Diseases of the domestic or wild goat of the genus Capra.
An adaptor protein, consisting of seven WD REPEATS along its length, that functions as a component of the MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1 and MTORC2 COMPLEX. It interacts directly with MTOR to enhance its kinase activity and stabilizes the MTOR-RPTOR PROTEIN interaction in nutrient-poor conditions, favoring RPTOR inhibition of MTOR activity.
Neoplasms of the endometrial stroma that sometimes involve the MYOMETRIUM. These tumors contain cells that may closely or remotely resemble the normal stromal cells. Endometrial stromal neoplasms are divided into three categories: (1) benign stromal nodules; (2) low-grade stromal sarcoma, or endolymphatic stromal myosis; and (3) malignant endometrial stromal sarcoma (SARCOMA, ENDOMETRIAL STROMAL).
A multiprotein complex consisting of MTOR KINASE; MLST8 PROTEIN; rapamycin-insensitive companion of mTOR protein (RICTOR PROTEIN); and PRR5 (proline-rich protein 5). Like MTORC1, it also regulates cell growth and proliferation in response to growth factors but may not be as sensitive to nutrient availability and is insensitive to SIROLIMUS. In contrast to MTORC1, it can regulate the ACTIN CYTOSKELETON through RHO GTPASES to promote the formation of STRESS FIBERS. The mTORC2 complex also plays a critical role in AKT1 PROTEIN KINASE phosphorylation and activation.
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Obstetrics and gynaecology
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