Loss of lamin B receptor is necessary to induce cellular
senescence

J 2017

Loss of lamin B receptor is necessary to induce cellular senescence

LUKÁŠOVÁ, Emilie, Aleš KOVAŘÍK, A BAČÍKOVÁ, Martin FALK, Stanislav KOZUBEK et. al.

Basic information

Original name

Loss of lamin B receptor is necessary to induce cellular senescence

Authors

LUKÁŠOVÁ, Emilie, Aleš KOVAŘÍK, A BAČÍKOVÁ, Martin FALK and Stanislav KOZUBEK

Edition

Biochemical Journal, 2017, 0264-6021

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Country of publisher

Czech Republic

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 3.857

DOI

http://dx.doi.org/10.1042/BCJ20160459

UT WoS

000393766200006

Abstract

V originále

Cellular transition to senescence is associated with extensive chromatin reorganization and changes in gene expression. Recent studies appear to imply an association of lamin B1 (LB1) reduction with chromatin rearrangement in human fibroblasts promoted to senescence, while the mechanisms and structural features of these relationships have not yet been clarified. In this work, we examined the functions of LB1 and the lamin B receptor (LBR) in human cancer cells. We found that both LB1 and LBR tend to deplete during cancer cell transfer to senescence by γ-irradiation. A functional study employing silencing of LBR by small hairpin ribonucleic acid (shRNA) constructs revealed reduced LB1 levels suggesting that the regulation of both proteins is interrelated. The reduced expression of LBR resulted in the relocation of centromeric heterochromatin (CSH) from the inner nuclear membrane (INM) to the nucleoplasm and is associated with its unfolding. This indicates that LBR tethers heterochromatin to INM in cycling cancer cells and that LB1 is an integral part of this tethering. Down-regulation of LBR and LB1 at the onset of senescence are thus necessary for the release of heterochromatin binding to lamina, resulting in changes in chromatin architecture and gene expression. However, the senescence phenotype was not manifested in cell lines with reduced LBR and LB1 expression suggesting that other factors, such as deoxyribonucleic acid (DNA) damage, are needed to trigger senescence. We conclude that the primary response of cells to various stresses leading to senescence consists of the down-regulation of LBR and LB1 to attain reversal of the chromatin architecture.

Links

GBP302/12/G157, research and development project

Name: Dynamika a organizace chromosomů během buněčného cyklu a při diferenciaci v normě a patologii

Investor: Czech Science Foundation

Citovat

LUKÁŠOVÁ, Emilie, Aleš KOVAŘÍK, A BAČÍKOVÁ, Martin FALK and Stanislav KOZUBEK. Loss of lamin B receptor is necessary to induce cellular senescence. Biochemical Journal. 2017, vol. 474, No 2, p. 281-300. ISSN 0264-6021. Available from: https://dx.doi.org/10.1042/BCJ20160459.

@article{1594206,
   author = {Lukášová, Emilie and Kovařík, Aleš and Bačíková, A and Falk, Martin and Kozubek, Stanislav},
   article_number = {2},
   doi = {http://dx.doi.org/10.1042/BCJ20160459},
   language = {eng},
   issn = {0264-6021},
   journal = {Biochemical Journal},
   title = {Loss of lamin B receptor is necessary to induce cellular senescence},
   url = {http://dx.doi.org/10.1042/BCJ20160459},
   volume = {474},
   year = {2017}
}

TY  - JOUR
ID  - 1594206
AU  - Lukášová, Emilie - Kovařík, Aleš - Bačíková, A - Falk, Martin - Kozubek, Stanislav
PY  - 2017
TI  - Loss of lamin B receptor is necessary to induce cellular senescence
JF  - Biochemical Journal
VL  - 474
IS  - 2
SP  - 281-300
EP  - 281-300
SN  - 02646021
UR  - http://dx.doi.org/10.1042/BCJ20160459
L2  - http://dx.doi.org/10.1042/BCJ20160459
N2  - Cellular transition to senescence is associated with extensive chromatin reorganization and changes in gene expression. Recent studies appear to imply an association of lamin B1 (LB1) reduction with chromatin rearrangement in human fibroblasts promoted to senescence, while the mechanisms and structural features of these relationships have not yet been clarified. In this work, we examined the functions of LB1 and the lamin B receptor (LBR) in human cancer cells. We found that both LB1 and LBR tend to deplete during cancer cell transfer to senescence by γ-irradiation. A functional study employing silencing of LBR by small hairpin ribonucleic acid (shRNA) constructs revealed reduced LB1 levels suggesting that the regulation of both proteins is interrelated. The reduced expression of LBR resulted in the relocation of centromeric heterochromatin (CSH) from the inner nuclear membrane (INM) to the nucleoplasm and is associated with its unfolding. This indicates that LBR tethers heterochromatin to INM in cycling cancer cells and that LB1 is an integral part of this tethering. Down-regulation of LBR and LB1 at the onset of senescence are thus necessary for the release of heterochromatin binding to lamina, resulting in changes in chromatin architecture and gene expression. However, the senescence phenotype was not manifested in cell lines with reduced LBR and LB1 expression suggesting that other factors, such as deoxyribonucleic acid (DNA) damage, are needed to trigger senescence. We conclude that the primary response of cells to various stresses leading to senescence consists of the down-regulation of LBR and LB1 to attain reversal of the chromatin architecture.
ER  -

LUKÁŠOVÁ, Emilie, Aleš KOVAŘÍK, A BAČÍKOVÁ, Martin FALK and Stanislav KOZUBEK. Loss of lamin B receptor is necessary to induce cellular senescence. \textit{Biochemical Journal}. 2017, vol.~474, No~2, p.~281-300. ISSN~0264-6021. Available from: https://dx.doi.org/10.1042/BCJ20160459.

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