Hsp70/Hsp90 chaperone machinery is involved in the assembly of the purinosome

• DOI: 10.1073/pnas.1300173110
• Publication Date: 2013-01-29T01:44:44Z
• Authors: Jarrod B. French; Hong Zhao; Songon An; Sherry Niessen; Yijun Deng; Benjamin F. Cravatt; Stephen J. Benkovic
• Keywords: Chaperone (clinical); Purine metabolism; Calnexin

The de novo biosynthesis of purines is carried out by a highly conserved metabolic pathway that includes several validated targets for anticancer, immunosuppressant, and anti-inflammatory chemotherapeutics. six enzymes in humans catalyze the 10 chemical steps from phosphoribosylpyrophosphate to inosine monophosphate were recently shown associate into dynamic multiprotein complex called purinosome. Here, we demonstrate heat shock protein 90 (Hsp90), 70 (Hsp70), cochaperones functionally colocalize with this complex. Knockdown expression levels identified leads disruption purinosomes. In addition, small molecule inhibitors Hsp90 Hsp70 reversibly disrupt purinosomes are have synergistic effect methotrexate, an anticancer agent purine biosynthesis. These data implicate Hsp90/Hsp70 chaperone machinery assembly purinosome provide strategy development improved therapies