Consequences of Lamin B1 and Lamin B Receptor Downregulation in Senescence

0492528 - BFÚ 2019 RIV CH eng J - Článek v odborném periodiku
Lukášová, Emilie - Kovařík, Aleš - Kozubek, Stanislav
Consequences of Lamin B1 and Lamin B Receptor Downregulation in Senescence.
Cells. Roč. 7, č. 2 (2018), č. článku 11. E-ISSN 2073-4409
Grant CEP: GA ČR GBP302/12/G157; GA ČR GBP501/12/G090
Klíčová slova: inner nuclear-membrane * oncogene-induced senescence * cellular senescence * heterochromatin formation * integral protein
Obor OECD: Cell biology
Impakt faktor: 5.656, rok: 2018

Anchoring of heterochromatin to the nuclear envelope appears to be an important process ensuring the spatial organization of the chromatin structure and genome function in eukaryotic nuclei. Proteins of the inner nuclear membrane (INM) mediating these interactions are able to recognize lamina-associated heterochromatin domains (termed LAD) and simultaneously bind either lamin A/C or lamin B1. One of these proteins is the lamin B receptor (LBR) that binds lamin B1 and tethers heterochromatin to the INM in embryonic and undifferentiated cells. It is replaced by lamin A/C with specific lamin A/C binding proteins at the beginning of cell differentiation and in differentiated cells. Our functional experiments in cancer cell lines show that heterochromatin in cancer cells is tethered to the INM by LBR, which is downregulated together with lamin B1 at the onset of cell transition to senescence. The downregulation of these proteins in senescent cells leads to the detachment of centromeric repetitive sequences from INM, their relocation to the nucleoplasm, and distension. In cells, the expression of LBR and LB1 is highly coordinated as evidenced by the reduction of both proteins in LBR shRNA lines. The loss of the constitutive heterochromatin structure containing LADs results in changes in chromatin architecture and genome function and can be the reason for the permanent loss of cell proliferation in senescence.
Trvalý link: http://hdl.handle.net/11104/0286029