Lamin B1 fluctuations have differential effects on cellular proliferation and senescence

Dreesen, Oliver; Chojnowski, Alexandre; Ong, P.P.; Zhao, Tian Yun; Common, John E.A.; Lunny, Declan P.; Lane, E. Birgitte; Lee, Shu Jin; Vardy, Leah A.; Stewart, Colin L.; Colman, Alan

doi:10.1084/jem2104oia2

Cited by 42 publications

(80 citation statements)

References 19 publications

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“…Lamin B3 is a minor splice variant of lamin B2 and is exclusively expressed in male germ cells (Furukawa and Hotta 1993). B-type lamins are involved in various cellular processes, including DNA replication (Moir et al 1994), cell cycle progression, chromatin remodelling and chromosome organisation (Moir et al 1994;Guelen et al 2008;Solovei et al 2013), mitotic spindle assembly (Tsai et al 2006;Kim et al 2011) and, as most recently found, senescence and ageing (Dreesen et al 2013a(Dreesen et al , 2013bShimi et al 2011;Freund et al 2012;Shah et al 2013;Sadaie et al 2013).…”

Section: A-type Laminsmentioning

confidence: 98%

“…We and others have developed cell-based in vitro models to study the consequences of lamin B1 overexpression on cell proliferation and function (Barascu et al 2012;Dreesen et al 2013aDreesen et al , 2013b. However, in human fibroblasts, a 2-to 3-fold overexpression of lamin B1 only results in a moderate proliferation defect.…”

Section: Diseases Associated With Perturbations Of B-type Laminsmentioning

confidence: 99%

“…Strikingly, lamin B1↑lamin A/C↓ cells exhibited a pronounced proliferation defect, arrested at the G0/G1 stage of the cell cycle and stained positive for senescence-associated-β-gal activity. In addition, lamin B1↑lamin A/C↓ cells exhibited 53BP-1 DNA damage foci that were associated with telomeres (Dreesen et al 2013a(Dreesen et al , 2013b. Reminiscent of the situation in progerin-expressing fibroblasts, the introduction of telomerase prevented the accumulation of telomeric DNA damage foci and restored the proliferation of lamin B1↑lamin A/C↓ cells (Dreesen et al 2013a, b).…”

Section: Diseases Associated With Perturbations Of B-type Laminsmentioning

confidence: 99%

“…The entry into senescence is associated with morphological changes, the expression of senescenceassociated β-galactosidase activity (SA-β-gal) and changes in gene expression and chromatin organisation, including the generation of senescence-associated heterochromatin foci and the senescence-associated secretory phenotype (Rodier and Campisi 2011). In addition, the nuclear lamina remodels dramatically as cells senesce (Dreesen et al 2013a(Dreesen et al , 2013bFreund et al 2012;Shimi et al 2011). These changes include a reduction of lamin B1 and the lamina associated polypeptide 2α (LAP2α).…”

Section: Lamina Remodelling In Cancer Cellsmentioning

confidence: 99%

“…The loss of lamin B1 levels is specific to senescent cells, whereas LAP2α levels also decline in quiescent cells. Loss of lamin B1 can additionally be used to identify senescent cells in vivo: lamin B1 levels decline in mice treated with a senescence-inducing dose of ionising radiation (Freund et al 2012), in a mouse model for the accelerated ageing syndrome progeria (McKenna et al 2014) and during the chronological ageing of human skin (Dreesen et al 2013a(Dreesen et al , 2013b. In addition to the loss of lamin B1, a reduced expression of lamin B1 receptor and a relocalisation of lamin A/C from the perinuclear region suggest that the nuclear envelope is structurally compromised in senescent cells (Ivanov et al 2013).…”

Section: Lamina Remodelling In Cancer Cellsmentioning

confidence: 99%

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Nuclear lamina remodelling and its implications for human disease

2014

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The intermediate filament A- and B-type lamins are key architectural components of the nuclear lamina, a proteinaceous meshwork that lies underneath the inner nuclear membrane. In the past decade, many different monogenic human diseases have been linked to mutations in various components of the nuclear lamina. Mutations in LMNA (encoding lamin A and C) cause a variety of human diseases, collectively called laminopathies. These include cardiomyopathies, muscular dystrophies, lipodystrophies and progeroid syndromes. In addition, elevated levels of lamin B1, attributable to genomic duplications of the LMNB1 locus, cause adult-onset autosomal dominant leukodystrophy. The molecular mechanism(s) enabling the mutations and perturbations of the nuclear lamina to give rise to such a wide variety of diseases that affect various tissues remains unclear. The composition of the nuclear lamina changes dynamically during development, between cell types and even within the same cell during differentiation and ageing. Here, we discuss the functional and cellular aspects of lamina remodelling and their implications for the tissue-specific nature of laminopathies.

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Section: A-type Laminsmentioning

confidence: 98%

Section: Diseases Associated With Perturbations Of B-type Laminsmentioning

confidence: 99%

Section: Diseases Associated With Perturbations Of B-type Laminsmentioning

confidence: 99%

Section: Lamina Remodelling In Cancer Cellsmentioning

confidence: 99%

Section: Lamina Remodelling In Cancer Cellsmentioning

confidence: 99%

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Nuclear lamina remodelling and its implications for human disease

2014

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Autophagy at the intersection of aging, senescence, and cancer

Cassidy

Narita

2022

Molecular Oncology

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Autophagy is an evolutionarily conserved cellular process in which macromolecules undergo lysosomal degradation. It fulfills essential roles in quality controlling cellular constituents and in energy homeostasis. Basal autophagy is also widely accepted to provide a protective role in aging and aging-related disorders, and its decline with age might precipitate the onset of a variety of diseases. In this review, we discuss the role of basal autophagy in maintaining homeostasis, in part through the maintenance of stem cell populations and the prevention of cellular senescence. We also consider how stress-induced senescence, for example, during oncogene activation and in premalignant disease, might rely on autophagy, and the possibility that the age-associated decline in autophagy might promote tumour development through a variety of mechanisms. Ultimately, evidence suggests that autophagy is required for malignant cancer progression in a number of settings. Thus, autophagy appears to be tumour-suppressive during the early stages of tumorigenesis and tumour-promoting at later stages.

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Aging mechanisms—A perspective mostly from Drosophila

Tsurumi

2020

Advanced Genetics

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A mechanistic understanding of the natural aging process, which is distinct from aging-related disease mechanisms, is essential for developing interventions to extend lifespan or healthspan. Here, we discuss current trends in aging research and address conceptual and experimental challenges in the field. We examine various molecular markers implicated in aging with an emphasis on the role of heterochromatin and epigenetic changes. Studies in model organisms have been advantageous in elucidating conserved genetic and epigenetic mechanisms and assessing interventions that affect aging. We highlight the use of Drosophila, which allows controlled studies for evaluating genetic and environmental contributors to aging conveniently. Finally, we propose the use of novel methodologies and future strategies using Drosophila in aging research.

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Lamin B1 fluctuations have differential effects on cellular proliferation and senescence

Cited by 42 publications

References 19 publications

Nuclear lamina remodelling and its implications for human disease

Nuclear lamina remodelling and its implications for human disease

Autophagy at the intersection of aging, senescence, and cancer

Aging mechanisms—A perspective mostly from Drosophila

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