| First Author | Levasseur EM | Year | 2019 |
| Journal | Sci Signal | Volume | 12 |
| Issue | 610 | PubMed ID | 31796630 |
| Mgi Jnum | J:286192 | Mgi Id | MGI:6402088 |
| Doi | 10.1126/scisignal.aax0715 | Citation | Levasseur EM, et al. (2019) Hypusine biosynthesis in beta cells links polyamine metabolism to facultative cellular proliferation to maintain glucose homeostasis. Sci Signal 12(610) |
| abstractText | Deoxyhypusine synthase (DHPS) uses the polyamine spermidine to catalyze the hypusine modification of the mRNA translation factor eIF5A and promotes oncogenesis through poorly defined mechanisms. Because germline deletion of Dhps is embryonically lethal, its role in normal postnatal cellular function in vivo remains unknown. We generated a mouse model that enabled the inducible, postnatal deletion of Dhps specifically in postnatal islet beta cells, which function to maintain glucose homeostasis. Removal of Dhps did not have an effect under normal physiologic conditions. However, upon development of insulin resistance, which induces beta cell proliferation, Dhps deletion caused alterations in proteins required for mRNA translation and protein secretion, reduced production of the cell cycle molecule cyclin D2, impaired beta cell proliferation, and induced overt diabetes. We found that hypusine biosynthesis was downstream of protein kinase C-zeta and was required for c-Myc-induced proliferation. Our studies reveal a requirement for DHPS in beta cells to link polyamines to mRNA translation to effect facultative cellular proliferation and glucose homeostasis. |
