Hypusine biosynthesis in β cells links polyamine metabolism to facultative cellular proliferation to maintain glucose homeostasis
dc.contributor.author | Levasseur, Esther M. | |
dc.contributor.author | Yamada, Kentaro | |
dc.contributor.author | Piñeros, Annie R. | |
dc.contributor.author | Wu, Wenting | |
dc.contributor.author | Syed, Farooq | |
dc.contributor.author | Orr, Kara S. | |
dc.contributor.author | Anderson-Baucum, Emily | |
dc.contributor.author | Mastracci, Teresa L. | |
dc.contributor.author | Maier, Bernhard | |
dc.contributor.author | Mosley, Amber L. | |
dc.contributor.author | Liu, Yunlong | |
dc.contributor.author | Bernal-Mizrachi, Ernesto | |
dc.contributor.author | Alonso, Laura C. | |
dc.contributor.author | Scott, Donald | |
dc.contributor.author | Garcia-Ocaña, Adolfo | |
dc.contributor.author | Tersey, Sarah A. | |
dc.contributor.author | Mirmira, Raghavendra G. | |
dc.contributor.department | Pediatrics, School of Medicine | en_US |
dc.date.accessioned | 2020-11-05T15:00:20Z | |
dc.date.available | 2020-11-05T15:00:20Z | |
dc.date.issued | 2019-12-03 | |
dc.description.abstract | Deoxyhypusine synthase (DHPS) utilizes 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 β 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 β-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 β-cell proliferation, and induced overt diabetes. We found that hypusine biosynthesis was downstream of protein kinase C-ζ and was required for c-Myc-induced proliferation. Our studies reveal a requirement for DHPS in β cells to link polyamines to mRNA translation to effect facultative cellular proliferation and glucose homeostasis. | en_US |
dc.eprint.version | Author's manuscript | en_US |
dc.identifier.citation | Levasseur, E. M., Yamada, K., Piñeros, A. R., Wu, W., Syed, F., Orr, K. S., Anderson-Baucum, E., Mastracci, T. L., Maier, B., Mosley, A. L., Liu, Y., Bernal-Mizrachi, E., Alonso, L. C., Scott, D., Garcia-Ocaña, A., Tersey, S. A., & Mirmira, R. G. (2019). Hypusine biosynthesis in β cells links polyamine metabolism to facultative cellular proliferation to maintain glucose homeostasis. Science Signaling, 12(610). https://doi.org/10.1126/scisignal.aax0715 | en_US |
dc.identifier.issn | 1945-0877, 1937-9145 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/24269 | |
dc.language.iso | en_US | en_US |
dc.publisher | American Association for the Advancement of Science | en_US |
dc.relation.isversionof | 10.1126/scisignal.aax0715 | en_US |
dc.relation.journal | Science Signaling | en_US |
dc.source | PMC | en_US |
dc.subject | RNA-Binding Proteins | en_US |
dc.subject | Polyamines | en_US |
dc.subject | Peptide Initiation Factors | en_US |
dc.subject | Insulin-Secreting Cells | en_US |
dc.subject | Glucose | en_US |
dc.subject | Lysine | en_US |
dc.title | Hypusine biosynthesis in β cells links polyamine metabolism to facultative cellular proliferation to maintain glucose homeostasis | en_US |
dc.type | Article | en_US |