Next Article in Journal
MiRNAs at the Crossroads between Innate Immunity and Cancer: Focus on Macrophages
Next Article in Special Issue
Autophagic Removal of Farnesylated Carboxy-Terminal Lamin Peptides
Previous Article in Journal
Optimization of Polycistronic Anti-CCR5 Artificial microRNA Leads to Improved Accuracy of Its Lentiviral Vector Transfer and More Potent Inhibition of HIV-1 in CD4+ T-Cells
Previous Article in Special Issue
Venture from the Interior—Herpesvirus pUL31 Escorts Capsids from Nucleoplasmic Replication Compartments to Sites of Primary Envelopment at the Inner Nuclear Membrane
Article Menu
Issue 2 (February) cover image

Export Article

Open AccessReview
Cells 2018, 7(2), 11; https://doi.org/10.3390/cells7020011

Consequences of Lamin B1 and Lamin B Receptor Downregulation in Senescence

1
Department of Cell Biology and Radiobiology, Institute of Biophysics, Czech Academy of Sciences, Královopolská 135, Brno 61265, Czech Republic
2
Department of Molecular Epigenetics, Institute of Biophysics, Czech Academy of Sciences, Královopolská 135, Brno 61265, Czech Republic
*
Author to whom correspondence should be addressed.
Received: 4 December 2017 / Revised: 24 January 2018 / Accepted: 31 January 2018 / Published: 6 February 2018
(This article belongs to the Collection Lamins and Laminopathies)
View Full-Text   |   Download PDF [533 KB, uploaded 14 March 2018]   |  

Abstract

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. View Full-Text
Keywords: lamin B receptor; lamin B1; lamin A/C; heterochromatin tether; constitutive heterochromatin; cellular senescence; centromere-specific satellite heterochromatin lamin B receptor; lamin B1; lamin A/C; heterochromatin tether; constitutive heterochromatin; cellular senescence; centromere-specific satellite heterochromatin
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

Lukášová, E.; Kovařík, A.; Kozubek, S. Consequences of Lamin B1 and Lamin B Receptor Downregulation in Senescence. Cells 2018, 7, 11.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cells EISSN 2073-4409 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top