OGT (O -GlcNAc Transferase) Selectively Modifies Multiple Residues Unique to Lamin A

Cells
Dan N SimonKatherine L Wilson

Abstract

The LMNA gene encodes lamins A and C with key roles in nuclear structure, signaling, gene regulation, and genome integrity. Mutations in LMNA cause over 12 diseases ('laminopathies'). Lamins A and C are identical for their first 566 residues. However, they form separate filaments in vivo, with apparently distinct roles. We report that lamin A is β-O-linked N-acetylglucosamine-(O-GlcNAc)-modified in human hepatoma (Huh7) cells and in mouse liver. In vitro assays with purified O-GlcNAc transferase (OGT) enzyme showed robust O-GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646), with no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails. Using mass spectrometry, we identified 11 O-GlcNAc sites in a 'sweet spot' unique to lamin A, with up to seven sugars per peptide. Most sites were unpredicted by current algorithms. Double-mutant (S612A/T643A) lamin A tails were still robustly O-GlcNAc-modified at seven sites. By contrast, O-GlcNAcylation was undetectable on tails bearing deletion Δ50, which causes Hutchinson⁻Gilford progeria syndrome, and greatly reduced by deletion Δ35. We conclude that residues deleted in progeria are required for substrate recognition and/or modification by OGT in vitro. I...Continue Reading

References

Nov 6, 1989·FEBS Letters·A FerraroC Turano
May 10, 2000·Proceedings of the National Academy of Sciences of the United States of America·R ShafiJ D Marth
Apr 10, 2003·Proceedings of the National Academy of Sciences of the United States of America·Jun LiuYosef Gruenbaum
May 4, 2004·Journal of Medical Genetics·K FukuchiT Ogihara
Oct 12, 2004·Journal of Proteome Research·Lewis Y GeerStephen H Bryant
Jan 14, 2005·Methods in Cell Biology·Harald HerrmannUeli Aebi
Feb 25, 2005·Proceedings of the National Academy of Sciences of the United States of America·Ayelet MargalitKatherine L Wilson
May 28, 2005·Diabetes·Jacques YoungCorinne Vigouroux
Dec 29, 2005·The Journal of Cell Biology·Melissa CrispDidier Hodzic
Aug 23, 2007·The Journal of Clinical Endocrinology and Metabolism·Aurélie DecaudainCorinne Vigouroux
Feb 8, 2008·The New England Journal of Medicine·Melissa A MeridethWendy J Introne
May 1, 2008·American Journal of Physiology. Endocrinology and Metabolism·Ronald J CopelandGerald W Hart
May 15, 2008·American Journal of Medical Genetics. Part a·Julia RankinSian Ellard
Jul 17, 2008·Angewandte Chemie·Mike SchutkowskiJens Schneider-Mergener
Jun 25, 2009·Autophagy·Young-Eun ParkIchizo Nishino
Nov 30, 2010·Cell·Gerald W Hart, Ronald J Copeland
Jun 7, 2011·Genome Biology·Travis A Dittmer, Tom Misteli
Jul 5, 2011·Human Molecular Genetics·Anne DutourPierre-Emmanuel Morange
Oct 6, 2011·Nature Reviews. Molecular Cell Biology·Dan N Simon, Katherine L Wilson
Dec 14, 2011·Nucleus·Annette Peter, Reimer Stick
Feb 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Hea-Jin JungLoren G Fong
Feb 23, 2012·PloS One·Jemima BarrowmanSusan Michaelis
Apr 21, 2012·Proceedings of the National Academy of Sciences of the United States of America·Joshua F AlfaroRichard D Smith
Jul 28, 2012·Science Translational Medicine·Jason C ChoiHoward J Worman
Sep 27, 2012·Proceedings of the National Academy of Sciences of the United States of America·Leslie B GordonMark W Kieran
Oct 10, 2012·Autophagy·Jason C Choi, Howard J Worman
Oct 16, 2012·Autophagy·Fresnida J RamosBrian K Kennedy
Dec 12, 2012·Nature·Qiang ChenXiaochun Yu
Mar 12, 2013·Chromosoma·Dan N Simon, Katherine L Wilson
May 7, 2013·Annual Review of Nutrition·Michelle R Bond, John A Hanover
Jul 31, 2013·Neurology·Nicole J UllrichMonica E Kleinman

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Citations

May 16, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Eric W LinM Bishr Omary
Apr 4, 2020·Genome Biology·Nolwenn Briand, Philippe Collas
Jan 9, 2021·Chemical Reviews·Junfeng MaGerald W Hart
Feb 10, 2021·Nature Cell Biology·Adam Karoutas, Asifa Akhtar
Jun 22, 2021·Trends in Biochemical Sciences·Laura A Murray-Nerger, Ileana M Cristea

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Methods Mentioned

BETA
pull-down
immunoprecipitation
glycosylation
two-hybrid

Software Mentioned

sWGA
Lasergene
Open Mass Spectrometry Search Algorithm ( OMSSA
ImageJ
OMSSA

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