Lamin A/C modulates spatial organization and function of the Hsp70 gene locus via nuclear myosin I

Pradhan, Roopali; Jayakrishnan, Muhunden; Sengupta, Kundan

doi:10.1242/jcs.236265

Cited by 15 publications

(17 citation statements)

References 105 publications

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“…As a result, mutations in the lamin genes cause a wide range of diseases called laminopathies, including Emery-Dreifuss muscular dystrophy and Hutchinson-Gilford progeria syndrome [8]. Furthermore, malfunctioning of lamins plays a role in diabetes, heat shock and cancer [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Addressing the Molecular Mechanism of Longitudinal Lamin Assembly Using Chimeric Fusions

Stalmans

Lilina

Vermeire

et al. 2020

Cells

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The molecular architecture and assembly mechanism of intermediate filaments have been enigmatic for decades. Among those, lamin filaments are of particular interest due to their universal role in cell nucleus and numerous disease-related mutations. Filament assembly is driven by specific interactions of the elementary dimers, which consist of the central coiled-coil rod domain flanked by non-helical head and tail domains. We aimed to investigate the longitudinal ‘head-to-tail’ interaction of lamin dimers (the so-called ACN interaction), which is crucial for filament assembly. To this end, we prepared a series of recombinant fragments of human lamin A centred around the N- and C-termini of the rod. The fragments were stabilized by fusions to heterologous capping motifs which provide for a correct formation of parallel, in-register coiled-coil dimers. As a result, we established crystal structures of two N-terminal fragments one of which highlights the propensity of the coiled-coil to open up, and one C-terminal rod fragment. Additional studies highlighted the capacity of such N- and C-terminal fragments to form specific complexes in solution, which were further characterized using chemical cross-linking. These data yielded a molecular model of the ACN complex which features a 6.5 nm overlap of the rod ends.

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Section: Introductionmentioning

confidence: 99%

Addressing the Molecular Mechanism of Longitudinal Lamin Assembly Using Chimeric Fusions

Stalmans

Lilina

Vermeire

et al. 2020

Cells

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“…Lamin A/C also plays a role in heat shock. Hsp70 protein binds and protects DNA in elevated temperatures and lamin A/C has been found to cause Hsp70 gene locus repositioning to the nuclear interior thus, it can be transcribed after heat shock [48].…”

Section: Lamin A/c: Role In Genomic Organization and Stabilitymentioning

confidence: 99%

Lamin A/C: Function in Normal and Tumor Cells

Dubik

Mai

2020

Cancers

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This review is focused on lamin A/C, a nuclear protein with multiple functions in normal and diseased cells. Its functions, as known to date, are summarized. This summary includes its role in maintaining a cell’s structural stability, cell motility, mechanosensing, chromosome organization, gene regulation, cell differentiation, DNA damage repair, and telomere protection. As lamin A/C has a variety of critical roles within the cell, mutations of the lamin A/C gene and incorrect processing of the protein results in a wide variety of diseases, ranging from striated muscle disorders to accelerated aging diseases. These diseases, collectively termed laminopathies, are also touched upon. Finally, we review the existing evidence of lamin A/C’s deregulation in cancer. Lamin A/C deregulation leads to various traits, including genomic instability and increased tolerance to mechanical insult, which can lead to more aggressive cancer and poorer prognosis. As lamin A/C’s expression in specific cancers varies widely, currently known lamin A/C expression in various cancers is reviewed. Additionally, Lamin A/C’s potential as a biomarker in various cancers and as an aid in more accurately diagnosing intermediate Gleason score prostate cancers is also discussed.

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“…The depletion of lamin B1 from the euchromatin fraction massively alters the expression profile of EMT (epithelial to mesenchymal transition)-associated genes (CDH1, FN1, ZEB1 and TWIST2), thereby resulting in impaired EMT [135,136]. Furthermore, nuclear lamins also contribute to altered gene expression during heat shock [137]. Lamin A/C depletion prevented the translocation of Hsp70 (a key transcription factor driving the expression of heat shock-induced genes during heat shock) into the nucleus upon heat shock ( Figure 3D).…”

Section: Lamins Modulate Gene Expressionmentioning

confidence: 99%

“…Lamin A/C depletion prevented the translocation of Hsp70 (a key transcription factor driving the expression of heat shock-induced genes during heat shock) into the nucleus upon heat shock ( Figure 3D). This uncovered a novel function for lamin A/C in modulating gene expression and the nuclear localization of the genomic locus of Hsp70 upon heat shock [137].…”

Section: Lamins Modulate Gene Expressionmentioning

confidence: 99%

Structure-Function Relationships of Nuclear Lamins

Patil¹,

Sengupta²

2020

Preprint

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Nuclear lamins are type V intermediate filament proteins that form a filamentous meshwork beneath the inner nuclear membrane. Additionally, a sub-population of A-type and B-type lamins is localized in the nuclear interior. The nuclear lamina protects the nucleus from mechanical stress and mediates nucleo-cytoskeletal coupling. Lamins form a scaffold that partially tethers chromatin at the nuclear envelope. The nuclear lamina also stabilizes protein-protein interactions involved in gene regulation and DNA repair. The lamin-based protein sub-complexes are implicated in both nuclear and cytoskeletal organization, the mechanical stability of the nucleus, genome organization, transcriptional regulation, genome stability, and cellular differentiation. Here we review recent research in the field of nuclear lamins and their role in modulating various nuclear processes and their impact on cell function.

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Lamin A/C modulates spatial organization and function of the Hsp70 gene locus via nuclear myosin I

Cited by 15 publications

References 105 publications

Addressing the Molecular Mechanism of Longitudinal Lamin Assembly Using Chimeric Fusions

Addressing the Molecular Mechanism of Longitudinal Lamin Assembly Using Chimeric Fusions

Lamin A/C: Function in Normal and Tumor Cells

Structure-Function Relationships of Nuclear Lamins

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