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Hypusine biosynthesis in β cells links polyamine metabolism to facultative cellular proliferation to maintain glucose homeostasis.

Citation
Levasseur, E. M., et al. “Hypusine Biosynthesis In Β Cells Links Polyamine Metabolism To Facultative Cellular Proliferation To Maintain Glucose Homeostasis.”. Science Signaling.
Center Indiana University University of Chicago
Multicenter
Multicenter
Author Esther M Levasseur, Kentaro Yamada, Annie R Piñeros, Wenting Wu, Farooq Syed, Kara S Orr, Emily Anderson-Baucum, Teresa L Mastracci, Bernhard Maier, Amber L Mosley, Yunlong Liu, Ernesto Bernal-Mizrachi, Laura C Alonso, Donald Scott, Adolfo Garcia-Ocaña, Sarah A Tersey, Raghavendra G Mirmira
Abstract

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 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 specifically in postnatal islet β cells, which function to maintain glucose homeostasis. Removal of did not have an effect under normal physiologic conditions. However, upon development of insulin resistance, which induces β cell proliferation, 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.

Year of Publication
2019
Journal
Science signaling
Volume
12
Issue
610
Date Published
12/2019
ISSN Number
1937-9145
DOI
10.1126/scisignal.aax0715
Alternate Journal
Sci Signal
PMID
31796630
PMCID
PMC7202401
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