scholarly journals Identification of ‘erasers’ for lysine crotonylated histone marks using a chemical proteomics approach

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Xiucong Bao ◽  
Yi Wang ◽  
Xin Li ◽  
Xiao-Meng Li ◽  
Zheng Liu ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Histone H3 ◽  
Gene Promoters ◽  
Biological Processes ◽  
Cellular Functions ◽  
Cellular Mechanisms ◽  
Chemical Proteomics ◽  
Wide Range ◽  
Proteomics Approach ◽  
Hydrolysis Of

Posttranslational modifications (PTMs) play a crucial role in a wide range of biological processes. Lysine crotonylation (Kcr) is a newly discovered histone PTM that is enriched at active gene promoters and potential enhancers in mammalian cell genomes. However, the cellular enzymes that regulate the addition and removal of Kcr are unknown, which has hindered further investigation of its cellular functions. Here we used a chemical proteomics approach to comprehensively profile ‘eraser’ enzymes that recognize a lysine-4 crotonylated histone H3 (H3K4Cr) mark. We found that Sirt1, Sirt2, and Sirt3 can catalyze the hydrolysis of lysine crotonylated histone peptides and proteins. More importantly, Sirt3 functions as a decrotonylase to regulate histone Kcr dynamics and gene transcription in living cells. This discovery not only opens opportunities for examining the physiological significance of histone Kcr, but also helps to unravel the unknown cellular mechanisms controlled by Sirt3, that have previously been considered solely as a deacetylase.

scholarly journals Signaling Specificity by Ras Family GTPases Is Determined by the Full Spectrum of Effectors They Regulate

2004 ◽  
Vol 24 (11) ◽  
pp. 4943-4954 ◽  
Author(s):  
Pablo Rodriguez-Viciana ◽  
Celine Sabatier ◽  
Frank McCormick
Keyword(s):  
Signaling Pathways ◽  
Differential Regulation ◽  
Biological Processes ◽  
Cellular Functions ◽  
Full Spectrum ◽  
Signaling Specificity ◽  
Related Family ◽  
Proteomics Approach ◽  
Ras Family ◽  
Differential Binding

ABSTRACT Ras family GTPases (RFGs) regulate signaling pathways that control multiple biological processes. How signaling specificity among the closely related family members is achieved is poorly understood. We have taken a proteomics approach to signaling by RFGs, and we have analyzed interactions of a panel of RFGs with a comprehensive group of known and potential effectors. We have found remarkable differences in the ability of RFGs to regulate the various isoforms of known effector families. We have also identified several proteins as novel effectors of RFGs with differential binding specificities to the various RFGs. We propose that specificity among RFGs is achieved by the differential regulation of combinations of effector families as well as by the selective regulation of different isoforms within an effector family. An understanding of this new level of complexity in the signaling pathways regulated by RFGs is necessary to understand how they carry out their many cellular functions. It will also likely have critical implications in the treatment of human diseases such as cancer.

scholarly journals Peptidyl Activity-Based Probes for Imaging Serine Proteases

2021 ◽  
Vol 9 ◽  
Author(s):  
Paulina Kasperkiewicz
Keyword(s):  
Posttranslational Modifications ◽  
Serine Proteases ◽  
Visual Observation ◽  
Biological Processes ◽  
Basic Principles ◽  
Peptide Bonds ◽  
Endogenous Inhibitors ◽  
Hydrolysis Of ◽  
Enormous Number

Proteases catalyze the hydrolysis of peptide bonds. Products of this breakdown mediate signaling in an enormous number of biological processes. Serine proteases constitute the most numerous group of proteases, accounting for 40%, and they are prevalent in many physiological functions, both normal and disease-related functions, making them one of the most important enzymes in humans. The activity of proteases is controlled at the expression level by posttranslational modifications and/or endogenous inhibitors. The study of serine proteases requires specific reagents not only for detecting their activity but also for their imaging. Such tools include inhibitors or substrate-related chemical molecules that allow the detection of proteolysis and visual observation of active enzymes, thus facilitating the characterization of the activity of proteases in the complex proteome. Peptidyl activity-based probes (ABPs) have been extensively studied recently, and this review describes the basic principles in the design of peptide-based imaging agents for serine proteases, provides examples of activity-based probe applications and critically discusses their strengths, weaknesses, challenges and limitations.

scholarly journals Quantitative H2S-mediated protein sulfhydration reveals metabolic reprogramming during the integrated stress response

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Xing-Huang Gao ◽  
Dawid Krokowski ◽  
Bo-Jhih Guan ◽  
Ilya Bederman ◽  
Mithu Majumder ◽  
...  
Keyword(s):  
Stress Response ◽  
Bioinformatics Analysis ◽  
Metabolic Reprogramming ◽  
Glycolytic Flux ◽  
Biological Processes ◽  
Integrated Stress Response ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Wide Range ◽  
Proteomics Approach

The sulfhydration of cysteine residues in proteins is an important mechanism involved in diverse biological processes. We have developed a proteomics approach to quantitatively profile the changes of sulfhydrated cysteines in biological systems. Bioinformatics analysis revealed that sulfhydrated cysteines are part of a wide range of biological functions. In pancreatic β cells exposed to endoplasmic reticulum (ER) stress, elevated H2S promotes the sulfhydration of enzymes in energy metabolism and stimulates glycolytic flux. We propose that transcriptional and translational reprogramming by the integrated stress response (ISR) in pancreatic β cells is coupled to metabolic alternations triggered by sulfhydration of key enzymes in intermediary metabolism.

scholarly journals Oxidative Stress in Fish: A Review

2020 ◽  
Vol 12 (1) ◽  
pp. 145-160 ◽  
Author(s):  
S. Chowdhury ◽  
S. K. Saikia
Keyword(s):  
Oxidative Stress ◽  
Environmental Factors ◽  
Metabolic Pathways ◽  
Energy Homeostasis ◽  
Enzymatic Antioxidants ◽  
Biological Processes ◽  
Stress Exposure ◽  
Cellular Functions ◽  
Atp Production ◽  
Wide Range

Apart from its beneficial properties of oxygen to cellular functions, it can cause some undesirable damages by the formation of ROS which can be neutralized by the formation of enzymatic and non-enzymatic antioxidants. Like any other vertebrate, these damages can be seen in fish which are exposed to various oxidative stressors. In fish, it may be brought by a variety of chemicals (pesticides, insecticides etc.), or environmental factors (DO, pH, temperature, salinity, etc) affecting different biological processes in fish. The present review discusses some of such stressors and their effects on fish from a wide range of literature available across last four decades. The metabolic pathways involved in terms of energy homeostasis and ATP production during stress exposure in fish is a new addition here, and has been addressed to some extent in case of temperature and salinity stress.

scholarly journals Phosphorylation-Dependent Targeting of Tetrahymena HP1 to Condensed Chromatin

mSphere ◽  
2016 ◽  
Vol 1 (4) ◽  
Author(s):  
Katerina Yale ◽  
Alan J. Tackett ◽  
Monica Neuman ◽  
Emily Bulley ◽  
Brian T. Chait ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Tetrahymena Thermophila ◽  
Chromatin Condensation ◽  
Histone H3 ◽  
Chromatin Protein ◽  
Ciliated Protozoan ◽  
Cellular Mechanisms ◽  
Content Type ◽  
Evolutionarily Conserved ◽  
Transcription And Replication

ABSTRACT Compacting the genome to various degrees influences processes that use DNA as a template, such as gene transcription and replication. This project was aimed at learning more about the cellular mechanisms that control genome compaction. Posttranslational modifications of proteins involved in genome condensation are emerging as potentially important points of regulation. To help elucidate protein modifications and how they affect the function of condensation proteins, we investigated the phosphorylation of the chromatin protein called Hhp1 in the ciliated protozoan Tetrahymena thermophila. This is one of the first functional investigations of these modifications of a nonhistone chromatin condensation protein that acts on the ciliate genome, and discoveries will aid in identifying common, evolutionarily conserved strategies that control the dynamic compaction of genomes. The evolutionarily conserved proteins related to heterochromatin protein 1 (HP1), originally described in Drosophila, are well known for their roles in heterochromatin assembly and gene silencing. Targeting of HP1 proteins to specific chromatin locales is mediated, at least in part, by the HP1 chromodomain, which binds to histone H3 methylated at lysine 9 that marks condensed regions of the genome. Mechanisms that regulate HP1 targeting are emerging from studies with yeast and metazoans and point to roles for posttranslational modifications. Here, we report that modifications of an HP1 homolog (Hhp1) in the ciliate model Tetrahymena thermophila correlated with the physiological state and with nuclear differentiation events involving the restructuring of chromatin. Results support the model in which Hhp1 chromodomain binds lysine 27-methylated histone H3, and we show that colocalization with this histone mark depends on phosphorylation at a single Cdc2/Cdk1 kinase site in the “hinge region” adjacent to the chromodomain. These findings help elucidate important functional roles of reversible posttranslational modifications of proteins in the HP1 family, in this case, regulating the targeting of a ciliate HP1 to chromatin regions marked with methylated H3 lysine 27. IMPORTANCE Compacting the genome to various degrees influences processes that use DNA as a template, such as gene transcription and replication. This project was aimed at learning more about the cellular mechanisms that control genome compaction. Posttranslational modifications of proteins involved in genome condensation are emerging as potentially important points of regulation. To help elucidate protein modifications and how they affect the function of condensation proteins, we investigated the phosphorylation of the chromatin protein called Hhp1 in the ciliated protozoan Tetrahymena thermophila. This is one of the first functional investigations of these modifications of a nonhistone chromatin condensation protein that acts on the ciliate genome, and discoveries will aid in identifying common, evolutionarily conserved strategies that control the dynamic compaction of genomes.

scholarly journals Tubulin glycylation controls axonemal dynein activity, flagellar beat, and male fertility

Science ◽  
2021 ◽  
Vol 371 (6525) ◽  
pp. eabd4914
Author(s):  
Sudarshan Gadadhar ◽  
Gonzalo Alvarez Viar ◽  
Jan Niklas Hansen ◽  
An Gong ◽  
Aleksandr Kostarev ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Male Fertility ◽  
Electron Tomography ◽  
Structural Basis ◽  
Cellular Functions ◽  
Flagellar Beat ◽  
Cryo Electron Tomography ◽  
Axonemal Dynein ◽  
Dynein Arms ◽  
Cilia And Flagella

Posttranslational modifications of the microtubule cytoskeleton have emerged as key regulators of cellular functions, and their perturbations have been linked to a growing number of human pathologies. Tubulin glycylation modifies microtubules specifically in cilia and flagella, but its functional and mechanistic roles remain unclear. In this study, we generated a mouse model entirely lacking tubulin glycylation. Male mice were subfertile owing to aberrant beat patterns of their sperm flagella, which impeded the straight swimming of sperm cells. Using cryo–electron tomography, we showed that lack of glycylation caused abnormal conformations of the dynein arms within sperm axonemes, providing the structural basis for the observed dysfunction. Our findings reveal the importance of microtubule glycylation for controlled flagellar beating, directional sperm swimming, and male fertility.

scholarly journals Effect of Posttranslational Modifications on the Structure and Activity of FTO Demethylase

2021 ◽  
Vol 22 (9) ◽  
pp. 4512
Author(s):  
Michał Marcinkowski ◽  
Tomaš Pilžys ◽  
Damian Garbicz ◽  
Jan Piwowarski ◽  
Damian Mielecki ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Size Exclusion Chromatography ◽  
Posttranslational Modifications ◽  
Size Exclusion ◽  
Saxs Data ◽  
Wide Range ◽  
Exclusion Chromatography ◽  
Demethylase Activity ◽  
Structure And Activity

The FTO protein is involved in a wide range of physiological processes, including adipogenesis and osteogenesis. This two-domain protein belongs to the AlkB family of 2-oxoglutarate (2-OG)- and Fe(II)-dependent dioxygenases, displaying N6-methyladenosine (N6-meA) demethylase activity. The aim of the study was to characterize the relationships between the structure and activity of FTO. The effect of cofactors (Fe2+/Mn2+ and 2-OG), Ca2+ that do not bind at the catalytic site, and protein concentration on FTO properties expressed in either E. coli (ECFTO) or baculovirus (BESFTO) system were determined using biophysical methods (DSF, MST, SAXS) and biochemical techniques (size-exclusion chromatography, enzymatic assay). We found that BESFTO carries three phosphoserines (S184, S256, S260), while there were no such modifications in ECFTO. The S256D mutation mimicking the S256 phosphorylation moderately decreased FTO catalytic activity. In the presence of Ca2+, a slight stabilization of the FTO structure was observed, accompanied by a decrease in catalytic activity. Size exclusion chromatography and MST data confirmed the ability of FTO from both expression systems to form homodimers. The MST-determined dissociation constant of the FTO homodimer was consistent with their in vivo formation in human cells. Finally, a low-resolution structure of the FTO homodimer was built based on SAXS data.

scholarly journals Energetics of mesoscale cell turbulence in two-dimensional monolayers

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Shao-Zhen Lin ◽  
Wu-Yang Zhang ◽  
Dapeng Bi ◽  
Bo Li ◽  
Xi-Qiao Feng
Keyword(s):  
Kinetic Energy ◽  
Tumor Metastasis ◽  
Cell Types ◽  
Boltzmann Distribution ◽  
Scaling Exponent ◽  
Biological Processes ◽  
Two Dimensional ◽  
Cell Monolayers ◽  
Wide Range ◽  
Epithelial Cell Monolayers

AbstractInvestigation of energy mechanisms at the collective cell scale is a challenge for understanding various biological processes, such as embryonic development and tumor metastasis. Here we investigate the energetics of self-sustained mesoscale turbulence in confluent two-dimensional (2D) cell monolayers. We find that the kinetic energy and enstrophy of collective cell flows in both epithelial and non-epithelial cell monolayers collapse to a family of probability density functions, which follow the q-Gaussian distribution rather than the Maxwell–Boltzmann distribution. The enstrophy scales linearly with the kinetic energy as the monolayer matures. The energy spectra exhibit a power-decaying law at large wavenumbers, with a scaling exponent markedly different from that in the classical 2D Kolmogorov–Kraichnan turbulence. These energetic features are demonstrated to be common for all cell types on various substrates with a wide range of stiffness. This study provides unique clues to understand active natures of cell population and tissues.

scholarly journals Recent development of nanoparticles for molecular imaging

2017 ◽  
Vol 375 (2107) ◽  
pp. 20170022 ◽  
Author(s):  
Jonghoon Kim ◽  
Nohyun Lee ◽  
Taeghwan Hyeon
Keyword(s):  
Surface Modification ◽  
Molecular Imaging ◽  
Contrast Agents ◽  
Multimodal Imaging ◽  
High Sensitivity ◽  
Accurate Diagnosis ◽  
Biological Processes ◽  
Future Perspectives ◽  
Cellular Functions ◽  
Diagnosis Of Diseases

Molecular imaging enables us to non-invasively visualize cellular functions and biological processes in living subjects, allowing accurate diagnosis of diseases at early stages. For successful molecular imaging, a suitable contrast agent with high sensitivity is required. To date, various nanoparticles have been developed as contrast agents for medical imaging modalities. In comparison with conventional probes, nanoparticles offer several advantages, including controllable physical properties, facile surface modification and long circulation time. In addition, they can be integrated with various combinations for multimodal imaging and therapy. In this opinion piece, we highlight recent advances and future perspectives of nanomaterials for molecular imaging. This article is part of the themed issue ‘Challenges for chemistry in molecular imaging’.

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