scholarly journals Histone H1 Post-Translational Modifications: Update and Future Perspectives

2020 ◽  
Vol 21 (16) ◽  
pp. 5941 ◽  
Author(s):  
Marta Andrés ◽  
Daniel García-Gomis ◽  
Inma Ponte ◽  
Pedro Suau ◽  
Alicia Roque
Keyword(s):  
Cell Cycle ◽  
Transcriptional Activation ◽  
Cellular Differentiation ◽  
Cell Types ◽  
Histone H1 ◽  
Molecular Function ◽  
Future Perspectives ◽  
Post Translational Modifications ◽  
Damage Response ◽  
Core Histones

Histone H1 is the most variable histone and its role at the epigenetic level is less characterized than that of core histones. In vertebrates, H1 is a multigene family, which can encode up to 11 subtypes. The H1 subtype composition is different among cell types during the cell cycle and differentiation. Mass spectrometry-based proteomics has added a new layer of complexity with the identification of a large number of post-translational modifications (PTMs) in H1. In this review, we summarize histone H1 PTMs from lower eukaryotes to humans, with a particular focus on mammalian PTMs. Special emphasis is made on PTMs, whose molecular function has been described. Post-translational modifications in H1 have been associated with the regulation of chromatin structure during the cell cycle as well as transcriptional activation, DNA damage response, and cellular differentiation. Additionally, PTMs in histone H1 that have been linked to diseases such as cancer, autoimmune disorders, and viral infection are examined. Future perspectives and challenges in the profiling of histone H1 PTMs are also discussed.

scholarly journals Differential activation of target cellular promoters by p53 mutants with impaired apoptotic function.

1996 ◽  
Vol 16 (9) ◽  
pp. 4952-4960 ◽  
Author(s):  
R L Ludwig ◽  
S Bates ◽  
K H Vousden
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Dna Sequences ◽  
Transcriptional Activation ◽  
Cellular Response ◽  
Kinase Inhibitor ◽  
Cell Types ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Cycle Arrest ◽  
P53 Tumor Suppressor Protein

The p53 tumor suppressor protein is a sequence-specific transcriptional activator, a function which contributes to cell cycle arrest and apoptosis induced by p53 in appropriate cell types. Analysis of a series of p53 point mutants has revealed the potential for selective loss of the ability to transactivate some, but not all, cellular p53-responsive promoters. p53 175P and p53 181L are tumor-derived p53 point mutants which were previously characterized as transcriptionally active. Both mutants retained the ability to activate expression of the cyclin-dependent kinase inhibitor p2lcip1/waf1, and this activity correlated with the ability to induce a G1 cell cycle arrest. However, an extension of this survey to include other p53 targets showed that p53 175P was defective in the activation of p53-responsive sequences derived from the bax promoter and the insulin-like growth factor-binding protein 3 gene (IGF-BP3) promoter, while p53 181L showed loss of the ability to activate a promoter containing IGF-BP3 box B sequences. Failure to activate transcription was also reflected in the reduced ability of the mutants to bind the p53-responsive DNA sequences present in these promoters. These specific defects in transcriptional activation correlated with the impaired apoptotic function displayed by these mutants, and the results suggest that activation of cell cycle arrest genes by p53 can be separated from activation of genes with a role in mediating the p53 apoptotic response. The cellular response to p53 activation may therefore depend, at least in part, on which group of p53-responsive genes become transcriptionally activated.

Lysine methylation and the regulation of p53

2012 ◽  
Vol 52 ◽  
pp. 79-92 ◽  
Author(s):  
Simon M. Carr ◽  
Shonagh Munro ◽  
Nicholas B. La Thangue
Keyword(s):  
Cell Cycle ◽  
Transcriptional Activation ◽  
Genotoxic Stress ◽  
Cellular Responses ◽  
Future Research ◽  
Lysine Methylation ◽  
Post Translational Modifications ◽  
Cycle Arrest ◽  
Tumour Suppressor Protein ◽  
Protein Functions

The p53 tumour suppressor protein functions as a guardian against genotoxic stress. This function is mediated in part by the transcriptional activation of genes involved in cell-cycle arrest, apoptosis, DNA repair and autophagy. The activity of p53 is regulated by a complex array of post-translational modifications, which function as a code to determine cellular responses to a given stress. In this chapter we highlight recent advances in our understanding of this code, with particular reference to lysine methylation, and discuss implications for future research.

Natural post-translational modifications of chemokines

2006 ◽  
Vol 34 (6) ◽  
pp. 997-1001 ◽  
Author(s):  
P. Proost ◽  
S. Struyf ◽  
J. Van Damme
Keyword(s):  
Transcriptional Activation ◽  
Chemokine Receptors ◽  
Cell Types ◽  
Proteolytic Processing ◽  
Fine Tuning ◽  
Specific Cell ◽  
Receptor Specificity ◽  
Post Translational Modifications ◽  
N Terminus ◽  
Acute And Chronic Inflammation

Chemokines, adhesion molecules, cytokines and proteases regulate the extravasation of leucocytes during acute and chronic inflammation and leucocyte homing. Chemokines are produced after transcriptional activation by inflammatory mediators such as cytokines or microbial Toll-like receptor ligands and their effect depends on the expression of chemokine receptors on specific cell types. More and more evidence points towards a role for post-translational modifications in the fine-tuning of chemokine activity. Although both glycosylation and proteolytic processing of the C- and/or N-terminus of chemokines has been reported, mainly proteolytic processing of the N-terminus appears to affect the receptor specificity, chemotactic property and signalling potency of these low-molecular-mass proteins. N-terminal processing of chemokines by aminopeptidases or endoproteases may alter the receptor specificity and may result in up- or down-regulation of their chemotactic, antiviral or angiogenic activity.

scholarly journals Histone H1 of Trypanosoma cruzi Is Concentrated in the Nucleolus Region and Disperses upon Phosphorylation during Progression to Mitosis

2008 ◽  
Vol 7 (4) ◽  
pp. 560-568 ◽  
Author(s):  
Luciana M. Gutiyama ◽  
Julia P. Chagas da Cunha ◽  
Sergio Schenkman
Keyword(s):  
Cell Cycle ◽  
Trypanosoma Cruzi ◽  
Cell Cycle Progression ◽  
Histone H1 ◽  
Nuclear Space ◽  
Dependent Manner ◽  
Central Regions ◽  
Core Histones ◽  
A Cell ◽  
Cycle Dependent

ABSTRACT Phosphorylation of histone H1 is intimately related to the cell cycle progression in higher eukaryotes, reaching maximum levels during mitosis. We have previously shown that in the flagellated protozoan Trypanosoma cruzi, which does not condense chromatin during mitosis, histone H1 is phosphorylated at a single cyclin-dependent kinase site. By using an antibody that recognizes specifically the phosphorylated T. cruzi histone H1 site, we have now confirmed that T. cruzi histone H1 is also phosphorylated in a cell cycle-dependent manner. Differently from core histones, the bulk of nonphosphorylated histone H1 in G1 and S phases of the cell cycle is concentrated in the central regions of the nucleus, which contains the nucleolus and less densely packed chromatin. When cells pass G2, histone H1 becomes phosphorylated and starts to diffuse. At the onset of mitosis, histone H1 phosphorylation is maximal and found in the entire nuclear space. As permeabilized parasites preferentially lose phosphorylated histone H1, we conclude that this modification promotes its release from less condensed and nucleolar chromatin after G2.

scholarly journals Identification of a novel calcitonin-response element in the promoter of the human p21WAF1/CIP1 gene

2000 ◽  
Vol 25 (2) ◽  
pp. 195-206 ◽  
Author(s):  
A Evdokiou ◽  
LJ Raggatt ◽  
T Sakai ◽  
DM Findlay
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Transcriptional Activation ◽  
Transmembrane Domain ◽  
Kinase Inhibitor ◽  
Cell Types ◽  
Hek 293 ◽  
Cycle Arrest ◽  
Cell Growth Suppression ◽  
P21 Promoter

The cyclin-dependent kinase inhibitor p21/WAF1/CIP1 is induced in many cell types in response to a variety of extracellular signals and causes cell cycle arrest in both the G1 and G2/M phases of the cell cycle. We reported previously that calcitonin (CT) receptor (CTR)-mediated growth inhibition of HEK-293 cells stably transfected with the human CTR is accompanied by a rapid and sustained induction of p21 and cell cycle arrest in G2. In the present study we have shown that CT stimulates transcription from a p21 promoter-luciferase construct. Using deletion and mutation analysis of the p21 promoter we have demonstrated that transcriptional activation of p21 by CT is p53-independent and is mediated through specific activation of Sp1-binding sites in a region of the promoter between -82 and -69, relative to the transcription start site. CTR-mediated transcriptional activation of p21 was specific for the insert-negative isoform of the human CTR. Butyrate, which was shown previously to activate the same Sp1 site, synergised with CT to increase further p21 promoter activity. These results provide the first demonstration that CTR can induce gene transcription through the constitutively expressed transcription factor Sp1, and define a mechanism of cell growth suppression that may have implications for other members of the seven-transmembrane domain G protein-coupled receptor superfamily.

scholarly journals Emerging roles of non-histone protein crotonylation in biomedicine

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jia-Yi Hou ◽  
Lan Zhou ◽  
Jia-Lei Li ◽  
De-Ping Wang ◽  
Ji-Min Cao
Keyword(s):  
Mass Spectrometry ◽  
Cell Cycle ◽  
Dna Damage ◽  
Gene Transcription ◽  
Dna Damage Response ◽  
Metabolic Pathways ◽  
Biological Functions ◽  
Histone Protein ◽  
Post Translational Modifications ◽  
Damage Response

AbstractCrotonylation of proteins is a newly found type of post-translational modifications (PTMs) which occurs leadingly on the lysine residue, namely, lysine crotonylation (Kcr). Kcr is conserved and is regulated by a series of enzymes and co-enzymes including lysine crotonyltransferase (writer), lysine decrotonylase (eraser), certain YEATS proteins (reader), and crotonyl-coenzyme A (donor). Histone Kcr has been substantially studied since 2011, but the Kcr of non-histone proteins is just an emerging field since its finding in 2017. Recent advances in the identification and quantification of non-histone protein Kcr by mass spectrometry have increased our understanding of Kcr. In this review, we summarized the main proteomic characteristics of non-histone protein Kcr and discussed its biological functions, including gene transcription, DNA damage response, enzymes regulation, metabolic pathways, cell cycle, and localization of heterochromatin in cells. We further proposed the performance of non-histone protein Kcr in diseases and the prospect of Kcr manipulators as potential therapeutic candidates in the diseases.

scholarly journals Clinical Candidates Targeting the ATR–CHK1–WEE1 Axis in Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 795
Author(s):  
Lukas Gorecki ◽  
Martin Andrs ◽  
Jan Korabecny
Keyword(s):  
Cell Cycle ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Patient Survival ◽  
Current Status ◽  
Future Perspectives ◽  
Phase Ii Trials ◽  
Anticancer Treatment ◽  
Positive Outlook ◽  
Insight Into

Selective killing of cancer cells while sparing healthy ones is the principle of the perfect cancer treatment and the primary aim of many oncologists, molecular biologists, and medicinal chemists. To achieve this goal, it is crucial to understand the molecular mechanisms that distinguish cancer cells from healthy ones. Accordingly, several clinical candidates that use particular mutations in cell-cycle progressions have been developed to kill cancer cells. As the majority of cancer cells have defects in G1 control, targeting the subsequent intra‑S or G2/M checkpoints has also been extensively pursued. This review focuses on clinical candidates that target the kinases involved in intra‑S and G2/M checkpoints, namely, ATR, CHK1, and WEE1 inhibitors. It provides insight into their current status and future perspectives for anticancer treatment. Overall, even though CHK1 inhibitors are still far from clinical establishment, promising accomplishments with ATR and WEE1 inhibitors in phase II trials present a positive outlook for patient survival.

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