PI3K/AKT/mTOR通路
环己酰亚胺
化学
磷酸化
RPTOR公司
基因敲除
信号转导
细胞生物学
蛋白质生物合成
分子生物学
基因
生物
生物化学
作者
Liping Xie,Rui Li,Jinlong Zhang,H M Li,Xuejun Gao,Minghui Zhang
标识
DOI:10.1021/acs.jafc.3c05370
摘要
Methionine (Met) functions as a key stimulator on the mTOR signaling pathway and milk synthesis, but the molecular mechanism remains incompletely understood. We investigated the regulatory roles of BRCC36 in Met-stimulated milk lipid and protein synthesis, cell proliferation, and the mTOR signaling pathway. Knockdown of BRCC36 promoted milk lipid and protein synthesis in HC11 cells as well as cell proliferation by increasing the levels of mTOR gene transcription and protein phosphorylation. Conversely, the gene activation of BRCC36 had opposite effects. Furthermore, BRCC36 gene activation completely blocked Met stimulation on the BRG1 protein level and mTOR mRNA level and protein phosphorylation. BRCC36 bound to BRG1, and BRCC36 and BRG1 bound to the same region on the mTOR promoter. BRCC36 inhibited the BRG1 protein level and the binding of BRG1 to the mTOR promoter. Met decreased the BRCC36 protein level, and this effect was significantly attenuated by MG132 but not affected by cycloheximide or chloroquine. We further showed that Met increased BRCC36 ubiquitination degradation. Our findings reveal that Met promotes milk lipid and protein synthesis in MECs through the BRCC36-BRG1-mTOR signaling axis.
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