Please use this identifier to cite or link to this item: https://doi.org/10.7554/eLife.07759
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dc.titleProgerin reduces LAP2?-telomere association in hutchinson-gilford progeria
dc.contributor.authorChojnowski, A
dc.contributor.authorOng, P.F
dc.contributor.authorWong, E.S.M
dc.contributor.authorLim, J.S.Y
dc.contributor.authorMutalif, R.A
dc.contributor.authorNavasankari, R
dc.contributor.authorDutta, B
dc.contributor.authorYang, H
dc.contributor.authorLiow, Y.Y
dc.contributor.authorSze, S.K
dc.contributor.authorBoudier, T
dc.contributor.authorWright, G.D
dc.contributor.authorColman, A
dc.contributor.authorBurke, B
dc.contributor.authorStewart, C.L
dc.contributor.authorDreesen, O
dc.date.accessioned2020-10-26T08:28:50Z
dc.date.available2020-10-26T08:28:50Z
dc.date.issued2015
dc.identifier.citationChojnowski, A, Ong, P.F, Wong, E.S.M, Lim, J.S.Y, Mutalif, R.A, Navasankari, R, Dutta, B, Yang, H, Liow, Y.Y, Sze, S.K, Boudier, T, Wright, G.D, Colman, A, Burke, B, Stewart, C.L, Dreesen, O (2015). Progerin reduces LAP2?-telomere association in hutchinson-gilford progeria. eLife 4 (42217) : Jan-21. ScholarBank@NUS Repository. https://doi.org/10.7554/eLife.07759
dc.identifier.issn2050084X
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/180322
dc.description.abstractHutchinson-Gilford progeria (HGPS) is a premature ageing syndrome caused by a mutation in LMNA, resulting in a truncated form of lamin A called progerin. Progerin triggers loss of the heterochromatic marker H3K27me3, and premature senescence, which is prevented by telomerase. However, the mechanism how progerin causes disease remains unclear. Here, we describe an inducible cellular system to model HGPS and find that LAP2? (lamina-associated polypeptide-?) interacts with lamin A, while its interaction with progerin is significantly reduced. Super-resolution microscopy revealed that over 50% of telomeres localize to the lamina and that LAP2? association with telomeres is impaired in HGPS. This impaired interaction is central to HGPS since increasing LAP2? levels rescues progerin-induced proliferation defects and loss of H3K27me3, whereas lowering LAP2 levels exacerbates progerin-induced defects. These findings provide novel insights into the pathophysiology underlying HGPS, and how the nuclear lamina regulates proliferation and chromatin organization. © 2015, eLife Sciences Publications Ltd. All Rights Reserved.
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20201031
dc.subjectdoxycycline
dc.subjectlamin A
dc.subjectlamin B
dc.subjectlamina associated polypeptide alpha
dc.subjectprogerin
dc.subjecttelomerase
dc.subjectunclassified drug
dc.subjectDNA binding protein
dc.subjectlamin A
dc.subjectlamina-associated polypeptide 2
dc.subjectmembrane protein
dc.subjectprelamin A
dc.subjectprotein binding
dc.subjectanimal cell
dc.subjectArticle
dc.subjectbiotinylation
dc.subjectcell differentiation
dc.subjectcell proliferation
dc.subjectchromatin
dc.subjectcontrolled study
dc.subjectDNA damage
dc.subjectgene mutation
dc.subjectheterochromatin
dc.subjectHutchinson Gilford progeria
dc.subjectimage analysis
dc.subjectimmunoblotting
dc.subjectimmunofluorescence
dc.subjectimmunofluorescence microscopy
dc.subjectimmunoprecipitation
dc.subjectmouse
dc.subjectnonhuman
dc.subjectprogeria
dc.subjectprotein expression
dc.subjectprotein interaction
dc.subjectprotein localization
dc.subjectprotein microarray
dc.subjectsenescence
dc.subjecthuman
dc.subjectmetabolism
dc.subjectmicroscopy
dc.subjectpathology
dc.subjectprogeria
dc.subjecttelomere
dc.subjectDNA-Binding Proteins
dc.subjectHumans
dc.subjectLamin Type A
dc.subjectMembrane Proteins
dc.subjectMicroscopy
dc.subjectProgeria
dc.subjectProtein Binding
dc.subjectTelomere
dc.typeArticle
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.contributor.departmentDEPT OF BIOLOGICAL SCIENCES
dc.description.doi10.7554/eLife.07759
dc.description.sourcetitleeLife
dc.description.volume4
dc.description.issue42217
dc.description.pageJan-21
dc.published.statePublished
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