scholarly journals Structure-Function Relationships of Nuclear Lamins

2020 ◽  
Author(s):  
Shalaka Patil ◽  
Kundan Sengupta
Keyword(s):  
Protein Interactions ◽  
Genome Stability ◽  
Cell Function ◽  
Mechanical Stability ◽  
Nuclear Lamina ◽  
Protein Protein Interactions ◽  
Intermediate Filament Proteins ◽  
Nuclear Lamins ◽  
Type V ◽  
Nuclear Processes

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.

scholarly journals Nuclear lamins and diabetes mellitus

STEMedicine ◽  
2020 ◽  
Vol 2 (5) ◽  
pp. e73
Author(s):  
Wei Xie ◽  
Brian Burke
Keyword(s):  
Diabetes Mellitus ◽  
Association Studies ◽  
Nuclear Lamina ◽  
Major Constituent ◽  
Genome Wide Association Studies ◽  
Intermediate Filament Proteins ◽  
Partial Lipodystrophy ◽  
Nuclear Lamins ◽  
Genes Encoding ◽  
Type V

In metazoans, a thin filamentous network referred to as the nuclear lamina plays an essential role in providing mechanical support to the nucleus. The major constituent of the nuclear lamina is type V intermediate filament proteins that are collectively referred to as lamins. A variety of diseases collectively termed laminopathies have been linked to mutations in genes encoding nuclear envelope proteins, in particular lamins, such as X-linked Emery Dreifus muscular dystrophy, dilated cardiomyopathy, Dunnigan type familial partial lipodystrophy and Hutchinson-Gilford progeria syndrome. Apart from laminopathies, genome-wide association studies have also been implicated nuclear lamins in the pathophysiology of type 2 diabetes mellitus, although little information in terms of the function of lamins in its pathogenesis. Our current review attempts to summarize risk factors of diabetes mellitus that could be attributable to lamin mutations and indirectly linked to lamin-associated factors identified in the last two decades.

The structure and function of the nuclear lamins

1995 ◽  
Vol 53 ◽  
pp. 762-763
Author(s):  
R.D. Goldman ◽  
A. Goldman ◽  
S. Khuon ◽  
M. Montag-Lowy ◽  
R. Moir ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Nuclear Lamina ◽  
Structure And Function ◽  
Supramolecular Organization ◽  
Intermediate Filament Proteins ◽  
Nuclear Envelope Breakdown ◽  
Nuclear Lamins ◽  
Interphase Cells ◽  
Type V ◽  
And Function

The nuclear lamins are the Type V intermediate filament proteins comprising the nuclear lamina. The lamina is located subjacent to the nucleoplasmic face of the nuclear envelope where it interfaces with chromatin. The lamins are major karyoskeletal proteins which are thought to play important roles in the formation and maintenance of nuclear shape and architecture, as well as in the supramolecular organization of chromatin. The lamins have long been thought to be stable polymeric constituents of the interphase nuclear matrix, due to their insolubility in solutions containing detergents and high salt concentrations. During mitosis, however, the nuclear lamins depolymerize during nuclear envelope breakdown. Subsequently, the lamins repolymerize around the decondensing chromosomes as the nuclear envelope reassembles at the end of mitosis. Although there is a significant amount known about the properties and potential functions of the lamins during mitosis, surprisingly little is known about their properties during interphase. In light of this, we have undertaken experiments which are aimed at determining the properties of the lamins in interphase cells.

scholarly journals Distinct p63 and p73 Protein Interactions Predict Specific Functions in mRNA Splicing and Polyploidy Control in Epithelia

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 25
Author(s):  
Julian M. Rozenberg ◽  
Olga S. Rogovaya ◽  
Gerry Melino ◽  
Nickolai A. Barlev ◽  
Alexander Kagansky
Keyword(s):  
Protein Interactions ◽  
Transcriptional Repression ◽  
Genome Stability ◽  
Spindle Assembly Checkpoint ◽  
Genotoxic Stress ◽  
Protein Protein Interactions ◽  
Proliferating Cells ◽  
P53 Family ◽  
Differentiated Cells ◽  
Specific Localization

Epithelial organs are the first barrier against microorganisms and genotoxic stress, in which the p53 family members p63 and p73 have both overlapping and distinct functions. Intriguingly, p73 displays a very specific localization to basal epithelial cells in human tissues, while p63 is expressed in both basal and differentiated cells. Here, we analyse systematically the literature describing p63 and p73 protein–protein interactions to reveal distinct functions underlying the aforementioned distribution. We have found that p73 and p63 cooperate in the genome stability surveillance in proliferating cells; p73 specific interactors contribute to the transcriptional repression, anaphase promoting complex and spindle assembly checkpoint, whereas p63 specific interactors play roles in the regulation of mRNA processing and splicing in both proliferating and differentiated cells. Our analysis reveals the diversification of the RNA and DNA specific functions within the p53 family.

scholarly journals The Role of Posttranslational Modifications in DNA Repair

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Miaomiao Bai ◽  
Dongdong Ti ◽  
Qian Mei ◽  
Jiejie Liu ◽  
Xin Yan ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Protein Interactions ◽  
Posttranslational Modifications ◽  
Genome Stability ◽  
Protein Localization ◽  
Complex Structure ◽  
Protein Protein Interactions ◽  
Regulate Protein

The human body is a complex structure of cells, which are exposed to many types of stress. Cells must utilize various mechanisms to protect their DNA from damage caused by metabolic and external sources to maintain genomic integrity and homeostasis and to prevent the development of cancer. DNA damage inevitably occurs regardless of physiological or abnormal conditions. In response to DNA damage, signaling pathways are activated to repair the damaged DNA or to induce cell apoptosis. During the process, posttranslational modifications (PTMs) can be used to modulate enzymatic activities and regulate protein stability, protein localization, and protein-protein interactions. Thus, PTMs in DNA repair should be studied. In this review, we will focus on the current understanding of the phosphorylation, poly(ADP-ribosyl)ation, ubiquitination, SUMOylation, acetylation, and methylation of six typical PTMs and summarize PTMs of the key proteins in DNA repair, providing important insight into the role of PTMs in the maintenance of genome stability and contributing to reveal new and selective therapeutic approaches to target cancers.

scholarly journals Arf•GAPs as Regulators of the Actin Cytoskeleton—An Update

2019 ◽  
Vol 20 (2) ◽  
pp. 442 ◽  
Author(s):  
Christine Tanna ◽  
Louisa Goss ◽  
Calvin Ludwig ◽  
Pei-Wen Chen
Keyword(s):  
Protein Interactions ◽  
Cell Function ◽  
Critical Role ◽  
Focal Adhesions ◽  
Actin Dynamics ◽  
Protein Protein Interactions ◽  
Post Translational Modification ◽  
Cellular Functions ◽  
Binding Domains ◽  
Multiple Protein

Arf•GTPase-activating proteins (Arf•GAPs) control the activity of ADP-ribosylation factors (Arfs) by inducing GTP hydrolysis and participate in a diverse array of cellular functions both through mechanisms that are dependent on and independent of their Arf•GAP activity. A number of these functions hinge on the remodeling of actin filaments. Accordingly, some of the effects exerted by Arf•GAPs involve proteins known to engage in regulation of the actin dynamics and architecture, such as Rho family proteins and nonmuscle myosin 2. Circular dorsal ruffles (CDRs), podosomes, invadopodia, lamellipodia, stress fibers and focal adhesions are among the actin-based structures regulated by Arf•GAPs. Arf•GAPs are thus important actors in broad functions like adhesion and motility, as well as the specialized functions of bone resorption, neurite outgrowth, and pathogen internalization by immune cells. Arf•GAPs, with their multiple protein-protein interactions, membrane-binding domains and sites for post-translational modification, are good candidates for linking the changes in actin to the membrane. The findings discussed depict a family of proteins with a critical role in regulating actin dynamics to enable proper cell function.

On the use of human autoantibodies in the determination of cytoskeletal-cell surface interactions

1991 ◽  
Vol 49 ◽  
pp. 16-17
Author(s):  
Robert D. Goldman ◽  
Jonathan C. R. Jones
Keyword(s):  
Cell Surface ◽  
Nuclear Lamina ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Nuclear Surface ◽  
Nuclear Lamins ◽  
Adhesion Sites ◽  
Cell Surface Interactions ◽  
Pore Complexes ◽  
Type V

Intermediate filaments (IF) form a cytoskeletal system which appears to connect the nuclear surface with the cell surface. At the level of the nuclear surface, IF appear to be anchored to the outer nuclear envelope membrane and/or to nuclear pore complexes. In turn, these cytoplasmic IF are also thought to be linked in some unknown fashion to the nuclear lamina which is composed primarily of a polymer of the Type V IF proteins, the nuclear lamins. At the level of the cell surface, IF are connected to plasma membrane associated structures at sites of cell-cell and cellsubstrate adhesion. In epithelial cells, adhesion sites between cells include desmosomes and the major adhesion sites between basal cell surfaces and the basement membrane are termed hemidesmosomes.

Purification and immunological detection of pea nuclear intermediate filaments: evidence for plant nuclear lamins

1992 ◽  
Vol 103 (2) ◽  
pp. 407-414 ◽  
Author(s):  
A.K. McNulty ◽  
M.J. Saunders
Keyword(s):  
Nuclear Envelope ◽  
Intermediate Filaments ◽  
Plant Cells ◽  
Nuclear Lamina ◽  
Animal Cells ◽  
Nuclear Lamins ◽  
Antigenic Characterization ◽  
Major Structural Component ◽  
Nuclear Envelope Assembly ◽  
Type V

A major structural component of the inner face of the nuclear envelope in vertebrates and invertebrates is the nuclear lamina, an array of 1–3 extrinsic membrane proteins, lamins A, B and C. These proteins are highly homologous to intermediate filaments and are classified as type V. We report the first purification, antigenic characterization and immunocytochemical localization of putative plant lamin proteins from pea nuclei. We conclude that plant cells contain this ancestral class of intermediate filaments in their nuclei and that regulation of nuclear envelope assembly/disassembly and mitosis in plants may be similar to that in animal cells.

scholarly journals Systematic identification of pathological lamin A interactors

2014 ◽  
Vol 25 (9) ◽  
pp. 1493-1510 ◽  
Author(s):  
Travis A. Dittmer ◽  
Nidhi Sahni ◽  
Nard Kubben ◽  
David E. Hill ◽  
Marc Vidal ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Global Scale ◽  
Premature Aging ◽  
Lamin A ◽  
Protein Protein Interactions ◽  
Systematic Map ◽  
Intermediate Filament Proteins ◽  
Tissue Specific ◽  
Interaction Sites ◽  
Premature Aging Syndromes

Laminopathies are a collection of phenotypically diverse diseases that include muscular dystrophies, cardiomyopathies, lipodystrophies, and premature aging syndromes. Laminopathies are caused by >300 distinct mutations in the LMNA gene, which encodes the nuclear intermediate filament proteins lamin A and C, two major architectural elements of the mammalian cell nucleus. The genotype–phenotype relationship and the basis for the pronounced tissue specificity of laminopathies are poorly understood. Here we seek to identify on a global scale lamin A–binding partners whose interaction is affected by disease-relevant LMNA mutations. In a screen of a human genome–wide ORFeome library, we identified and validated 337 lamin A–binding proteins. Testing them against 89 known lamin A disease mutations identified 50 disease-associated interactors. Association of progerin, the lamin A isoform responsible for the premature aging disorder Hutchinson–Gilford progeria syndrome, with its partners was largely mediated by farnesylation. Mapping of the interaction sites on lamin A identified the immunoglobulin G (IgG)–like domain as an interaction hotspot and demonstrated that lamin A variants, which destabilize the Ig-like domain, affect protein–protein interactions more globally than mutations of surface residues. Analysis of a set of LMNA mutations in a single residue, which result in three phenotypically distinct diseases, identified disease-specific interactors. The results represent a systematic map of disease-relevant lamin A interactors and suggest loss of tissue-specific lamin A interactions as a mechanism for the tissue-specific appearance of laminopathic phenotypes.

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