摘要
Lipid metabolism,in particular fatty acid and cholesterol synthesis,is essential to convert nutrients into metabolic intermediates for membrane biosynthesis,energy storage and the generation of signaling molecules.Tumor cells maintain high level of lipid metabolism for rapid cell proliferation[1-4].Transcription of genes required for fatty acid and cholesterol synthesis and cholesterol uptake is controlled by membrane-bound transcription factor sterol regulatory element-binding proteins(SREBPs),including SREBP-1a,SREBP-1c/ADD1 and SREBP-2 isoforms[5].The function of SREBPs is mainly regulated by an escort protein(the SREBP cleavage-activating protein[SCAP])and endoplasmic reticulum(ER)anchor proteins(insulininduced genes[Insigs]),during the feedback loop of cholesterol synthesis[6-8].Under sterol-depleted conditions,SCAP and SREBPs complex is captured by COPIImediated vesicles and transported from the ER to the Golgi apparatus[7,9],where the SREBPs are proteolytically processed by Site-1 protease(S1P)and Site-2 protease(S2P)to yield active amino-terminal fragments that enter the nucleus for gene transcription[10,11].Under high intracellular sterol conditions,abundant cholesterol in the ER membrane binds to SCAP,induces its conformational change,and enables it to bind to Insigs.
