Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/180322
Title: Progerin reduces LAP2?-telomere association in hutchinson-gilford progeria
Authors: Chojnowski, 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
Keywords: doxycycline
lamin A
lamin B
lamina associated polypeptide alpha
progerin
telomerase
unclassified drug
DNA binding protein
lamin A
lamina-associated polypeptide 2
membrane protein
prelamin A
protein binding
animal cell
Article
biotinylation
cell differentiation
cell proliferation
chromatin
controlled study
DNA damage
gene mutation
heterochromatin
Hutchinson Gilford progeria
image analysis
immunoblotting
immunofluorescence
immunofluorescence microscopy
immunoprecipitation
mouse
nonhuman
progeria
protein expression
protein interaction
protein localization
protein microarray
senescence
human
metabolism
microscopy
pathology
progeria
telomere
DNA-Binding Proteins
Humans
Lamin Type A
Membrane Proteins
Microscopy
Progeria
Protein Binding
Telomere
Issue Date: 2015
Citation: Chojnowski, 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.
Rights: Attribution 4.0 International
Abstract: Hutchinson-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.
Source Title: eLife
URI: https://scholarbank.nus.edu.sg/handle/10635/180322
ISSN: 2050084X
Rights: Attribution 4.0 International
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