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Akan I, Halim A, Vakhrushev SY, Clausen H, Hanover JA. Drosophila O-GlcNAcase Mutants Reveal an Expanded Glycoproteome and Novel Growth and Longevity Phenotypes. Cells 2021 10(5) 33925313
The reversible posttranslational O-GlcNAc modification of serine or threonine residues of intracellular proteins is involved in many cellular events from signaling cascades to epigenetic and transcriptional regulation. O-GlcNAcylation is a conserved nutrient-dependent process involving two enzymes, with O-GlcNAc transferase (OGT) adding O-GlcNAc and with O-GlcNAcase (OGA) removing it in a manner that's protein- and context-dependent. O-GlcNAcylation is essential for epigenetic regulation of gene expression through its action on Polycomb and Trithorax and COMPASS complexes. However, the important role of O-GlcNAc in adult life and health span has been largely unexplored, mainly due the lack of available model systems. Cataloging the O-GlcNAc proteome has proven useful in understanding the biology of this modification in vivo. In this study, we leveraged a recently developed oga knockout fly mutant to identify the O-GlcNAcylated proteins in adult Drosophilamelanogaster. The adult O-GlcNAc proteome revealed many proteins related to cell and organismal growth, development, differentiation, and epigenetics. We identified many O-GlcNAcylated proteins that play a role in increased growth and decreased longevity, including HCF, SIN3A, LOLA, KISMET, ATX2, SHOT, and FOXO. Interestingly, oga mutant flies are larger and have a shorter life span compared to wild type flies, suggesting increased O-GlcNAc results in increased growth. Our results suggest that O-GlcNAc alters the function of many proteins related to transcription, epigenetic modification and signaling pathways that regulate growth rate and longevity. Therefore, our findings highlight the importance of O-GlcNAc in growth and life span in adult Drosophila.
O-GlcNAc proteins:
A0A0B4K6K9, A0A0B4K6N5, A0A0B4K6T1, A0A0B4K707, A0A0B4K7Q3, A0A0B4K7V4, A0A0B4K813, A0A0B4K880, A0A0B4KF23, A0A0B4KGY9, A0A0B4KHB2, A0A0B4KI71, A0A0B4LF93, A0A0B4LFP7, A0A0B4LFX4, A0A0B4LGJ1, A0A0B4LGL0, A0A0B4LH23, A0A0B4LH64, A0A0B4LHK4, A0A0B4LHS9, A0A0B4LIF3, A0A0B4LJ24, PO210, A1Z6M0, A1Z7F1, A1Z7Y7, A1Z8Z3, A1Z9J3, A1Z9L2, A8DQW8, SBNO, B7Z049, B7Z0L0, B7Z0Q5, E1JHV7, E2QCS7, G3JX32, M9MRJ4, M9MRN7, M9MS77, M9NCQ1, M9NE59, M9NEL3, M9NG31, M9NG33, M9NGK3, M9PCF6, M9PCJ8, M9PCM8, M9PCM8, M9PDU2, M9PE74, M9PEK8, M9PFU6, M9PI47, M9PI58, M9PI84, M9PJ79, O61380, O96607, RPB1, OPS1, L2GL, CO4A1, LAMB1, ITBX, LSP1G, ITA2, PDE4B, FSH, CYPR, DHGL, SUZ2, GLT, MNB, STIM, YL, LAMA, Q0E8B8, MESH, LSP2, SYN, Q5BIJ2, Q6GV06, SODE, Q7JWQ7, NUP62, NUP50, Q7K1C5, Q7K3Y9, Q7K3Z3, SCRIB, Q7KTJ7, LOLA4, PPN, Q86BM5, Q8IHB0, Q8IMB8, Q8IMH4, Q8INE9, Q8IPG9, TRR, LBR, Q8MMD3, Q8MRI4, Q8SWX4, Q8SX98, Q8SXR1, Q8T0N3, Q8T3W8, Q95R71, GILT1, Q95RC5, FOXO, CAPR1, Q9I7M5, Q9I7S9, LAR4, Q9I7T8, PATJ, CAPS, ERO1L, Q9V3U6, Q9V4B8, HCF, NUP54, Q9V9U1, CTNS, Q9VCR9, Q9VCS4, Q9VDI1, Q9VDT5, Q9VFC9, Q9VFR2, Q9VG78, Q9VH63, Q9VHC3, Q9VHC8, Q9VIF2, Q9VII5, Q9VJQ3, Q9VJX4, EDC4, Q9VKM8, Q9VKP2, Q9VKT1, Q9VLF4, Q9VM55, Q9VMD2, TIG, Q9VMV5, Q9VP57, Q9VPQ7, Q9VPU9, Q9VQ58, Q9VQM0, INE, Q9VR69, Q9VRT5, Q9VS02, Q9VSC3, Q9VT00, Q9VTC1, PLOD, Q9VTW7, NPLP2, Q9VUH6, Q9VUJ4, Q9VVP9, Q9VW34, Q9VWL4, MINY3, Q9VXA3, NU153, Q9VXH7, MADD, Q9VXY5, Q9VY04, Q9VYR1, Q9VZ58, Q9VZJ3, Q9VZQ7, Q9W1A9, Q9W1J0, NU214, Q9W2N6, Q9W329, Q9W3F3, Q9W3G1, Q9W3L4, Q9W3V9, Q9W451, Q9W4M7, FUTSC, Q9W5B4, Q9Y0Z1, Q9Y136, Q9Y141, Q9Y154, R9PY26, X2JAR4, X2JC54, X2JG40, X2JIM3
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