Identification of the lamin A/C phosphoepitope recognized by the antibody P-STM in mitotic HeLa S3 cells

Chen, Jeng-Ting; Ho, Chia-Wen; Chi, Lang‐Ming; Chien, Kun-Yi; Hsieh, Ya-Ju; Lin, Shio Jean; Yu, Jau‐Song

doi:10.1186/1471-2091-14-18

Cited by 14 publications

(13 citation statements)

References 34 publications

(47 reference statements)

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“…Phosphorylation of lamins and their partners has been shown to be important for NE breakdown at the beginning of mitosis [40,41]. Two serine residues of lamin A and C are substrates for AKT kinase, activated by several signaling pathways [42], the phosphorylation of serine 404 leading to prelamin A autophagic degradation [43].…”

Section: Other Post-translational Modifications Of Laminsmentioning

confidence: 99%

Nuclear matrix, nuclear envelope and premature aging syndromes in a translational research perspective

Cau

Navarro

Harhouri

et al. 2014

Seminars in Cell & Developmental Biology

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Lamin A-related progeroid syndromes are genetically determined, extremely rare and severe. In the past ten years, our knowledge and perspectives for these diseases has widely progressed, through the progressive dissection of their pathophysiological mechanisms leading to precocious and accelerated aging, from the genes mutations discovery until therapeutic trials in affected children. A-type lamins are major actors in several structural and functional activities at the nuclear periphery, as they are major components of the nuclear lamina. However, while this is usually poorly considered, they also play a key role within the rest of the nucleoplasm, whose defects are related to cell senescence. Although nuclear shape and nuclear envelope deformities are obvious and visible events, nuclear matrix disorganization and abnormal composition certainly represent the most important causes of cell defects with dramatic pathological consequences. Therefore, lamin-associated diseases should be better referred as laminopathies instead of envelopathies, this later being too restrictive, considering neither the key structural and functional roles of soluble lamins in the entire nucleoplasm, nor the nuclear matrix contribution to the pathophysiology of lamin-associated disorders and in particular in defective lamin A processing-associated aging diseases. Based on both our understanding of pathophysiological mechanisms and the biological and clinical consequences of progeria and related diseases, therapeutic trials have been conducted in patients and were terminated less than 10 years after the gene discovery, a quite fast issue for a genetic disease. Pharmacological drugs have been repurposed and used to decrease the toxicity of the accumulated, unprocessed and truncated prelaminA in progeria. To date, none of them may be considered as a cure for progeria and these clinical strategies were essentially designed toward reducing a subset of the most dramatic and morbid features associated to progeria. New therapeutic strategies under study, in particular targeting the protein expression pathway at the mRNA level, have shown a remarkable efficacy both in vitro in cells and in vivo in mice models. Strategies intending to clear the toxic accumulated proteins from the nucleus are also under evaluation. However, although exceedingly rare, improving our knowledge of genetic progeroid syndromes and searching for innovative and efficient therapies in these syndromes is of paramount importance as, even before they can be used to save lives, they may significantly (i) expand the affected childrens' lifespan and preserve their quality of life; (ii) improve our understanding of aging-related disorders and other more common diseases; and (iii) expand our fundamental knowledge of physiological aging and its links with major physiological processes such as those involved in oncogenesis.

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Section: Other Post-translational Modifications Of Laminsmentioning

confidence: 99%

Nuclear matrix, nuclear envelope and premature aging syndromes in a translational research perspective

Cau

Navarro

Harhouri

et al. 2014

Seminars in Cell & Developmental Biology

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“…Such spatial organization is considerably supported by the nuclear lamina, suggesting a significant role for the lamina in genome organization . Lamins are direct targets of CDKs , an interaction which results in their disassembly and solubilization during nuclear envelope breakdown at mitosis . Therefore, resurrecting the lamina–chromatin association upon nuclear envelope reformation could represent another challenge following mitotic exit.…”

Section: Challenges Associated With Copying the Complex Epigenomementioning

confidence: 99%

Cell cycle dynamics in the reprogramming of cellular identity

Eastman

Guo

2019

FEBS Letters

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Reprogramming of cellular identity is fundamentally at odds with replication of the genome: cell fate reprogramming requires complex multidimensional epigenomic changes, whereas genome replication demands fidelity. In this review, we discuss how the pace of the genome's replication and cell cycle influences the way daughter cells take on their identity. We highlight several biochemical processes that are pertinent to cell fate control, whose propagation into the daughter cells should be governed by more complex mechanisms than simple templated replication. With this mindset, we summarize multiple scenarios where rapid cell cycle could interfere with cell fate copying and promote cell fate reprogramming. Prominent examples of cell fate regulation by specific cell cycle phases are also discussed. Overall, there is much to be learned regarding the relationship between cell fate reprogramming and cell cycle control. Harnessing cell cycle dynamics could greatly facilitate the derivation of desired cell types.

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“…The canonical phosphoacceptor serine residue is very conserved. For H. sapiens , it is located at position S22 in lamin A/C [ 23 , 37 – 39 ], S23 in lamin B1 [ 30 ] and S37 in lamin B2 [ 40 ]. For X. laevis , the positions are S18, S23, S27 and S21 for lamins A, B1, B2 and B3, respectively.…”

Section: Sequence Conservation and Phosphorylation In The Head Domainmentioning

confidence: 99%

“…The similar, conservative motif in most lamins (T19PL in human lamin A, S42PT in fly lamin Dm) also contains strong consensus sequences for Cdk5, Gsk3 and ERK1–2 kinases. Phosphorylation of this site has been discovered experimentally ( figure 2 ; electronic supplementary material, table S1) [ 23 , 31 , 37 , 39 ] and in many large-scale proteomics studies (electronic supplementary material, table S2 for references).…”

Section: Sequence Conservation and Phosphorylation In The Head Domainmentioning

confidence: 99%

“…Proximal to the end of the rod domain lies the C-terminal ‘mitotic’ cdc2 (Cdk1) site, crucial for lamin polymerization and depolymerization (with the exception of Ce-lamin). This region contains conservative phosphoacceptor serine residues, which in H. sapiens are located at positions S390 and S392 in lamin A/C [ 23 , 37 – 39 ], S391 and S393 in lamin B1, and S405 and S407 in lamin B2 [ 40 ] ( figure 3 ). In Xenopus , the predicted phosphoacceptor residues are S386/388, S391/393 and S395/397 for lamins A, B1 and B2, respectively.…”

Section: Sequence Conservation and Phosphorylation In The Tail Domainmentioning

confidence: 99%

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Regulation of lamin properties and functions: does phosphorylation do it all?

Machowska¹,

Piekarowicz²,

Rzepecki³

2015

Open Biol.

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The main functions of lamins are their mechanical and structural roles as major building blocks of the karyoskeleton. They are also involved in chromatin structure regulation, gene expression, intracellular signalling pathway modulation and development. All essential lamin functions seem to depend on their capacity for assembly or disassembly after the receipt of specific signals, and after specific, selective and precisely regulated interactions through their various domains. Reversible phosphorylation of lamins is crucial for their functions, so it is important to understand how lamin polymerization and interactions are modulated, and which sequences may undergo such modifications. This review combines experimental data with results of our in silico analyses focused on lamin phosphorylation in model organisms to show the presence of evolutionarily conserved sequences and to indicate specific in vivo phosphorylations that affect particular functions.

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Identification of the lamin A/C phosphoepitope recognized by the antibody P-STM in mitotic HeLa S3 cells

Cited by 14 publications

References 34 publications

Nuclear matrix, nuclear envelope and premature aging syndromes in a translational research perspective

Nuclear matrix, nuclear envelope and premature aging syndromes in a translational research perspective

Cell cycle dynamics in the reprogramming of cellular identity

Regulation of lamin properties and functions: does phosphorylation do it all?

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