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Loss of lamin B receptor is necessary to induce cellular senescence
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SYSNO ASEP 0485752 Druh ASEP J - Článek v odborném periodiku Zařazení RIV Záznam nebyl označen do RIV Poddruh J Článek ve WOS Název Loss of lamin B receptor is necessary to induce cellular senescence Tvůrce(i) Lukášová, Emilie (BFU-R) RID, ORCID
Kovařík, Aleš (BFU-R) RID, ORCID
Bačíková, Alena (BFU-R)
Falk, Martin (BFU-R) RID, ORCID
Kozubek, Stanislav (BFU-R) RIDCelkový počet autorů 5 Zdroj.dok. Biochemical Journal. - : Portland Press - ISSN 0264-6021
Roč. 474 (2017), s. 281-300Poč.str. 20 s. Forma vydání Tištěná - P Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova oncogene-induced senescence ; inner nuclear-membrane ; dna-damage response Vědní obor RIV EB - Genetika a molekulární biologie Obor OECD Genetics and heredity (medical genetics to be 3) CEP GBP302/12/G157 GA ČR - Grantová agentura ČR GBP501/12/G090 GA ČR - Grantová agentura ČR Institucionální podpora BFU-R - RVO:68081707 UT WOS 000393766200006 DOI 10.1042/BCJ20160459 Anotace 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 gamma-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. Pracoviště Biofyzikální ústav Kontakt Jana Poláková, polakova@ibp.cz, Tel.: 541 517 244 Rok sběru 2018
Počet záznamů: 1