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Data suggest that HMGCS1 (HMG-CoA synthase 1) signals through ketogenesis/acetoacetate to promote cell proliferation and BRAF (show BRAF Proteins)(V600E)-dependent MEK1 (show MAP2K1 Proteins) activation in BRAF (show BRAF Proteins)(V600E)-positive melanoma and colon cancer cells; HMGCS1 co-localizes with HMGCL (HMG-CoA lyase (show HMGCL Proteins)) and BRAF (show BRAF Proteins)(V600E) in cytosol of melanoma and colon cancer cells. (BRAF (show BRAF Proteins) = proto-oncogene (show RAB1A Proteins) protein B (show LEPREL2 Proteins)-raf (show SNRPE Proteins))
ACBP (show CPN2 Proteins) is a transcriptional regulator of the HMGCS1 and HMGCR (show HMGCR Proteins) genes encoding rate-limiting enzymes of cholesterol synthesis pathway.
Mutation of hmgcs1 had no effect on Shh (show SHH Proteins) signaling at 2 and 3 days post fertilization (dpf), but did result in a decrease in the expression of gli1 (show GLI1 Proteins), a known Shh (show SHH Proteins) target gene, at 4 dpf, after morphological deficits in craniofacial development and chondrocyte differentiation were observed in hmgcs1 mutants.
This study identified a mutation of hmgcs1, coding for Hmg-CoA synthase (show HMGCS2 Proteins) 1, which caused OPCs to migrate past their target axons and interfered with myelin gene expression.
This enzyme condenses acetyl-CoA with acetoacetyl-CoA to form HMG-CoA, which is the substrate for HMG-CoA reductase.
3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase
, 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 (soluble)
, hydroxymethylglutaryl-CoA synthase, cytoplasmic
, 3-hydroxy-3-methylglutaryl-CoA synthase 1 (soluble)
, 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 (soluble) isoform 1
, 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 (soluble) isoform 2
, 3-hydroxy-3-methylglutaryl coenzyme A synthase
, HMG-CoA synthase
, hydroxymethylglutaryl-CoA synthase 1
, hydroxymethylglutaryl coenzyme A synthase
, hydroxymethylglutaryl-CoA synthase, cytoplasmic-like