====== SCAP ======
Sterol regulatory element-binding protein cleavage-activating protein, also known as [[SREBP]] cleavage-activating protein or [[SCAP]] is a protein that in humans is encoded by the SCAP gene. SCAP contains a sterol-sensing domain and seven WD domains.
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[[Ammonia]] activates the dissociation of [[glucose]]-regulated, N-glycosylated SREBP-cleavage-activating protein ([[SCAP]]) from insulin-inducible gene protein ([[Insig]]), an endoplasmic reticulum-retention protein, leading to [[SREBP]] translocation and lipogenic gene expression. Notably, 25-hydroxycholesterol blocks ammonia to access its binding site on SCAP. Mutating aspartate D428 to alanine prevents ammonia binding to SCAP, abolishes SREBP-1 activation, and suppresses tumor growth. The study of Cheng et al. characterizes the unknown role, opposite to [[sterol]]s, of [[ammonia]] as a key activator that stimulates [[SCAP]]-Insig dissociation and [[SREBP]]-1 activation to promote tumor growth and demonstrates that SCAP is a critical sensor of [[glutamine]], [[glucose]], and sterol levels to precisely control lipid synthesis
((Cheng C, Geng F, Li Z, Zhong Y, Wang H, Cheng X, Zhao Y, Mo X, Horbinski C, Duan W, Chakravarti A, Cheng X, Guo D. Ammonia stimulates SCAP/Insig dissociation and SREBP-1 activation to promote lipogenesis and tumour growth. Nat Metab. 2022 May 9. doi: 10.1038/s42255-022-00568-y. Epub ahead of print. PMID: 35534729.)).