Lamin B receptor (LBR) is involved in the induction of cellular senescence in human cells

Arai, Rumi; En, Atsuki; Takauji, Yuki; Maki, Kazuhiro; Miki, Kensuke; Fujii, Michihiko; Ayusawa, Dai

doi:10.1016/j.mad.2019.01.001

Cited by 17 publications

(21 citation statements)

References 39 publications

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“…In addition to protein accumulation, a body of evidence indicates that dysregulation of chromatin has a role in cellular senescence [17]. Consistent with this, we have previously found that lamin B receptor (LBR), a nuclear membrane protein that regulates heterochromatin organization [18], shows aberrant localization and down-regulation in senescent cells [19,20]. In addition, we showed that knockdown of LBR induces cellular senescence in TIG-7 cells [20].…”

supporting

confidence: 73%

“…Then protein accumulation induced cellular senescence through the down‐regulation of LBR function. Notably, we have also shown the crucial roles of LBR in cellular senescence by the findings that knockdown of LBR induces cellular senescence in TIG‐7 cells and facilitates the induction of cellular senescence by excess thymidine in HeLa cells . In addition, we explored the regulatory mechanism of LBR and found that ER stress and autophagy that are induced by MG132 were likely involved in the mislocalization and down‐regulation of LBR in senescent cells.…”

Section: Discussionmentioning

confidence: 81%

“…We have previously shown that mislocalization and down‐regulation of LBR are observed in BrdU‐induced, excess thymidine‐induced, and replicative senescent cells . We then examined the localization of LBR in the cells treated with MG132, and found that they showed a similar change in the localization of LBR; that is, proliferating cells showed a normal nuclear peripheral localization pattern of LBR, but MG132‐treated cells showed a diffusive distribution pattern of it (Fig.…”

Section: Resultsmentioning

confidence: 87%

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Lamin B receptor plays a key role in cellular senescence induced by inhibition of the proteasome

Takauji

Miki

et al. 2020

FEBS Open Bio

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Cellular senescence is a terminal growth arrest phenomenon in mammalian cells. Coordinated regulation of protein synthesis and degradation is required to maintain protein homeostasis in cells; however, senescent cells exhibit decreased activity of the proteasome, a major cellular proteolytic machinery, with an accumulation of proteins. Indeed, we showed that MG132, a proteasome inhibitor, induced cellular senescence through an accumulation of proteins in human cells. We then investigated the mechanisms of cellular senescence induced by protein accumulation by treating cells with MG132. We found that lamin B receptor (LBR), a nuclear membrane protein that regulates heterochromatin organization, was mislocalized and down‐regulated in cells on treatment with MG132. Importantly, enforced expression of LBR suppressed cellular senescence induced by MG132. We also showed that LBR was involved in the regulation of chromatin organization in senescent cells, and that endoplasmic reticulum stress and autophagy were likely to be involved in the mislocalization and down‐regulation of LBR. These findings indicate that decreased LBR function was responsible for the induction of cellular senescence by MG132, and thus suggest that protein accumulation caused by inhibition of the proteasome induced cellular senescence probably through chromatin dysregulation in human cells.

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supporting

confidence: 73%

Section: Discussionmentioning

confidence: 81%

Section: Resultsmentioning

confidence: 87%

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Lamin B receptor plays a key role in cellular senescence induced by inhibition of the proteasome

Takauji

Miki

et al. 2020

FEBS Open Bio

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“…A number of studies have indicated that chromatin and chromatin proteins are involved in cellular senescence (113,114). For example, the altered expression of lamins A/C and B, which form the nuclear lamina, as well as altered heterochromatin structures have been observed in senescent cells (115,116). In addition, the expression of lamin B1 (LB1) in WI-38 cells was found to decrease during cellular senescence, and the silencing of LB1 slowed the proliferation of these cells and induced premature senescence.…”

Section: Lamin B Receptor (Lbr)mentioning

confidence: 99%

Possibility of inducing tumor cell senescence during therapy (Review)

et al. 2021

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“…NADs remain very similar in replicative senescent embryonic fibroblasts ( Dillinger et al, 2017 ). However, some LADs are released from the nuclear edge with the loss of lamin B receptor ( Arai et al, 2019 ) and lamin B1 in senescence ( Shimi et al, 2011 ; Freund et al, 2012 ; Hutchison, 2012 ; Lukášová et al, 2017 , 2018 ). Indeed, chromosome 18 is less attached to the nucleoskeleton than chromosomes 1, 13, 17 in replicative senescent cells, as is CTNNA1 gene compared to CNDD1 (cyclin D1) ( Godwin et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Interphase Chromosomes in Replicative Senescence: Chromosome Positioning as a Senescence Biomarker and the Lack of Nuclear Motor-Driven Chromosome Repositioning in Senescent Cells

Mehta

Riyahi

Pereira

et al. 2021

Front. Cell Dev. Biol.

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This study demonstrates, and confirms, that chromosome territory positioning is altered in primary senescent human dermal fibroblasts (HDFs). The chromosome territory positioning pattern is very similar to that found in HDFs made quiescent either by serum starvation or confluence; but not completely. A few chromosomes are found in different locations. One chromosome in particular stands out, chromosome 10, which is located in an intermediate location in young proliferating HDFs, but is found at the nuclear periphery in quiescent cells and in an opposing location of the nuclear interior in senescent HDFs. We have previously demonstrated that individual chromosome territories can be actively and rapidly relocated, with 15 min, after removal of serum from the culture media. These chromosome relocations require nuclear motor activity through the presence of nuclear myosin 1β (NM1β). We now also demonstrate rapid chromosome movement in HDFs after heat-shock at 42°C. Others have shown that heat shock genes are actively relocated using nuclear motor protein activity via actin or NM1β (Khanna et al., 2014; Pradhan et al., 2020). However, this current study reveals, that in senescent HDFs, chromosomes can no longer be relocated to expected nuclear locations upon these two types of stimuli. This coincides with a entirely different organisation and distribution of NM1β within senescent HDFs.

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Lamin B receptor (LBR) is involved in the induction of cellular senescence in human cells

Cited by 17 publications

References 39 publications

Lamin B receptor plays a key role in cellular senescence induced by inhibition of the proteasome

Lamin B receptor plays a key role in cellular senescence induced by inhibition of the proteasome

Possibility of inducing tumor cell senescence during therapy (Review)

Interphase Chromosomes in Replicative Senescence: Chromosome Positioning as a Senescence Biomarker and the Lack of Nuclear Motor-Driven Chromosome Repositioning in Senescent Cells

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