Fig. 3

Role of p53 in regulating the mevalonate pathway. Acetate can be converted to acetyl-CoA, which can then enter the mevalonate pathway and be further converted into 3-hydroxy-3-methylglutaryl CoA in a two-step synthesis (HMG-CoA). Then, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) reduces HMG-CoA to provide mevalonate. Then, mevalonate can control the enzymatic processes that lead to protein prenylation. Sterol regulatory element binding proteins (SREBPs) can interact with p53 mutants to promote the expression of mevalonate pathway genes. On the other hand, as a result of the transcriptional upregulation of ATP binding cassette subfamily A member 1, wild type p53 (WT p53) represses the genes involved in the mevalonate pathway by preventing SREBP-2 from maturing (ABCA1). Additionally, while WT p53 acts as a transcriptional repressor, mutant p53 can activate the isoprenylcysteine carboxyl methyltransferase (ICMT) gene. The final stage of the protein prenylation pathway, protein carboxymethylation, is catalyzed by ICMT. The rate-limiting reaction, which is carried out by the enzyme methionine adenosyl transferase, converts the important amino acid methionine into S-adenosyl methionine (SAM), the methyl donor in this reaction (MAT). S-adenosyl homocysteine (SAH), which is needed in the methionine cycle to replenish methionine, is created when SAM is converted. Ras upregulation by amyloid p53 might activate several other signaling networks controlling differentiation, survival, and cell proliferation