Fig. 2: Control of p53 function by non-canonical functions of metabolic enzymes. | Experimental & Molecular Medicine

Fig. 2: Control of p53 function by non-canonical functions of metabolic enzymes.

From: Non-canonical functions of enzymes facilitate cross-talk between cell metabolic and regulatory pathways

Fig. 2: Control of p53 function by non-canonical functions of metabolic enzymes.

In response to DNA damage, guanosine 5’-monophosphate synthase (GMPS) shifts from a complex containing the E3 ligase TRIM21 to interaction with the deubiquitylating enzyme USP7. This leads to deubiquitylation of GMPS and allows its translocation to the nucleus, where it replaces MDM2 and stabilizes p53 to promote cell cycle arrest and apoptosis. Upon glucose starvation, malate dehydrogenase 1 (MDH1) activates p53 by binding to the p53/MDM2 complex and preventing ubiquitylation and cytoplasmic retention of p53. IMP inosine monophosphate; XMP xanthosine monophosphate; GMP guanosine 5’-monophosphate; GDP guanosine 5’-diphosphate; GTP guanosine 5’-triphosphate

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