SEC61G (SEC61 Translocon Subunit Gamma)

In addition, Exo-miR-488-3p tended to induce HepG2 cells apoptosis, though this relationship was not statistically significant. In conclusion, exo-miR-488-3p inhibits the malignant cytological activities in HCC, a possible strategy in the treatment of HCC.

Sdcbp and Rpl22 were most abundantly expressed in Microglia, and Ppia in Oligodendrocytes, while Sec61g exhibited lower overall expression, all showing high activity in immune metabolic pathways. Bioinformatics analysis and experimental verification indicate that Sdcbp, Ppia, and Sec61g are associated with ferroptosis and immune infiltration in IS, and hold promise as therapeutic targets for IS treatment.

This study provides the first comprehensive analysis of the role of SEC61G in pan-cancer and cervical squamous cell carcinoma and adenocarcinoma. Our findings suggest that SEC61G can serve as a diagnostic biomarker and prognostic indicator for cervical cancers.

Upon DNA damage induction (right panel), enhanced interaction between BRCA1 and PARP13 attenuates the mRNA degradation activity of PARP13 toward SEC61G, leading to upregulated SEC61G protein expression. The aberrant accumulation of SEC61G triggers endoplasmic reticulum calcium leakage, which subsequently activates the AKT signaling pathway to enhance cell survival capacity.

Consequently, inhibiting these proteins leads to a crisis in proliferation and/or survival. Additionally, our data suggests that Ipom-F may act as an immunosuppressive agent.

Using this method, we select small molecules capable of hampering the protein expression of the PD-L1 immune checkpoint by interfering with its ER translocation and delivering it for degradation. In conclusion, our screening method will greatly facilitate the selection of Sec61 inhibitors for down-modulating the expression of many disease-relevant proteins.

SIGNIFICANCE STATEMENT: KZR-834 and KZR-261 are novel Sec61 inhibitors with the ability to block multiple Sec61 client proteins, leading to well-tolerated efficacy in in vivo cancer models. This represents a novel mechanism for blocking expression of oncogenic factors, including those not amenable to targeting through conventional methods.

Furthermore, the tested microsome samples responded well to the translocation inhibitor cyclotriazadisulfonamide in suppressing human CD4 protein translocation into the ER. In conclusion, microsomes isolated from frozen canine pancreatic tissue proved to retain their co-translational translocation functionality that can contribute to our research of Sec61-dependent protein translocation and selective inhibition thereof.

This review describes the structure of Sec61 and its function in transporting ER transmembrane proteins and further summarizes the role of this gene in disease and recent advancements in Sec61 inhibitors. This study provides novel insights into the involvement of Sec61 in disease etiology and lays the groundwork for future treatment modalities targeting this pivotal protein complex.

SEC61G promotes CRC progression by regulating cytosolic Ca2+ concentration, EGFR activation, and cell cycle progression, highlighting its potential as a prognostic biomarker and therapeutic target in CRC.

Through Morris water maze test, LTP test, Western blot (WB), immunohistochemistry (IHC), mitochondrial observation under electron microscope, calcium ion concentration measurement and mitochondrial membrane potential measurement, it was found that AOAA could not only regulate the level of endoplasmic reticulum stress (ERS) caused by H2S elevation, but also maintain the role of valve of Sec61 channel on Ca2+ by restoring the level of BIP, a key indicator of ERS, significantly alleviate mitochondrial dysfunction caused by Ca2+ overload, and optimize learning and memory function. The mechanism may be closely related to the BDNF-TrkB pathway.