scholarly journals Regulation of Root Nutrient Transporters by CIPK23: ‘One Kinase to Rule Them All’

2020 ◽  
Author(s):  
Reyes Ródenas ◽  
Grégory Vert
Keyword(s):  
Protein Kinases ◽  
Molecular Mechanisms ◽  
Potassium Nitrate ◽  
Nutrient Transporters ◽  
Interacting Protein ◽  
Cellular Processes ◽  
Iron Metal ◽  
Nutrient Imbalances ◽  
Root Responses ◽  
Phosphate Groups

Abstract Protein kinases constitute essential regulatory components in the majority of cellular processes in eukaryotic cells. The CBL-INTERACTING PROTEIN KINASE (CIPK) family of plant protein kinases functions in calcium (Ca2+)-related signaling pathways and is therefore involved in the response to a wide variety of signals in plants. By covalently linking phosphate groups to their target proteins, CIPKs regulate the activity of downstream targets, their localization, their stability and their ability to interact with other proteins. In Arabidopsis, the CIPK23 kinase has emerged as a major hub driving root responses to diverse environmental stresses, including drought, salinity and nutrient imbalances, such as potassium, nitrate and iron deficiencies, as well as ammonium, magnesium and non-iron metal toxicities. This review will chiefly report on the prominent roles of CIPK23 in the regulation of plant nutrient transporters and on the underlying molecular mechanisms. We will also discuss the different scenarios explaining how a single promiscuous kinase, such as CIPK23, may convey specific responses to a myriad of signals.

scholarly journals MeCP2-E1 isoform is a dynamically expressed, weakly DNA-bound protein with different protein and DNA interactions compared to MeCP2-E2

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Alexia Martínez de Paz ◽  
Leila Khajavi ◽  
Hélène Martin ◽  
Rafael Claveria-Gimeno ◽  
Susanne Tom Dieck ◽  
...  
Keyword(s):  
Rett Syndrome ◽  
Cellular Localization ◽  
Molecular Mechanisms ◽  
Amino Acid Residues ◽  
Proteomics Data ◽  
Specific Expression ◽  
Interacting Protein ◽  
Cellular Processes ◽  
Specific Regulation ◽  
Dynamics Response

Abstract Background MeCP2—a chromatin-binding protein associated with Rett syndrome—has two main isoforms, MeCP2-E1 and MeCP2-E2, differing in a few N-terminal amino acid residues. Previous studies have shown brain region-specific expression of these isoforms which, in addition to their different cellular localization and differential expression during brain development, suggest that they may also have non-overlapping molecular mechanisms. However, differential functions of MeCP2-E1 and E2 remain largely unexplored. Results Here, we show that the N-terminal domains (NTD) of MeCP2-E1 and E2 modulate the ability of the methyl-binding domain (MBD) to interact with DNA as well as influencing the turn-over rates, binding dynamics, response to neuronal depolarization, and circadian oscillations of the two isoforms. Our proteomics data indicate that both isoforms exhibit unique interacting protein partners. Moreover, genome-wide analysis using ChIP-seq provide evidence for a shared as well as a specific regulation of different sets of genes. Conclusions Our study supports the idea that Rett syndrome might arise from simultaneous impairment of cellular processes involving non-overlapping functions of MECP2 isoforms. For instance, MeCP2-E1 mutations might impact stimuli-dependent chromatin regulation, while MeCP2-E2 mutations could result in aberrant ribosomal expression. Overall, our findings provide insight into the functional complexity of MeCP2 by dissecting differential aspects of its two isoforms.

scholarly journals Pathophysiological Roles of Stress-Activated Protein Kinases in Pulmonary Fibrosis

2021 ◽  
Vol 22 (11) ◽  
pp. 6041
Author(s):  
Yoshitoshi Kasuya ◽  
Jun-Dal Kim ◽  
Masahiko Hatano ◽  
Koichiro Tatsumi ◽  
Shuichi Matsuda
Keyword(s):  
Pulmonary Fibrosis ◽  
Protein Kinases ◽  
Molecular Mechanisms ◽  
Alveolar Epithelial Cells ◽  
Mitogen Activated Protein Kinase ◽  
Sequencing Data ◽  
Alveolar Epithelial ◽  
Cellular Processes ◽  
Mitogen Activated Protein ◽  
Fibrotic Lung Diseases

Idiopathic pulmonary fibrosis (IPF) is one of the most symptomatic progressive fibrotic lung diseases, in which patients have an extremely poor prognosis. Therefore, understanding the precise molecular mechanisms underlying pulmonary fibrosis is necessary for the development of new therapeutic options. Stress-activated protein kinases (SAPKs), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38) are ubiquitously expressed in various types of cells and activated in response to cellular environmental stresses, including inflammatory and apoptotic stimuli. Type II alveolar epithelial cells, fibroblasts, and macrophages are known to participate in the progression of pulmonary fibrosis. SAPKs can control fibrogenesis by regulating the cellular processes and molecular functions in various types of lung cells (including cells of the epithelium, interstitial connective tissue, blood vessels, and hematopoietic and lymphoid tissue), all aspects of which remain to be elucidated. We recently reported that the stepwise elevation of intrinsic p38 signaling in the lungs is correlated with a worsening severity of bleomycin-induced fibrosis, indicating an importance of this pathway in the progression of pulmonary fibrosis. In addition, a transcriptome analysis of RNA-sequencing data from this unique model demonstrated that several lines of mechanisms are involved in the pathogenesis of pulmonary fibrosis, which provides a basis for further studies. Here, we review the accumulating evidence for the spatial and temporal roles of SAPKs in pulmonary fibrosis.

scholarly journals Role of Long Non-Coding RNA Polymorphisms in Cancer Chemotherapeutic Response

2021 ◽  
Vol 11 (6) ◽  
pp. 513
Author(s):  
Zheng Zhang ◽  
Meng Gu ◽  
Zhongze Gu ◽  
Yan-Ru Lou
Keyword(s):  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Cellular Processes ◽  
Dna And Rna ◽  
Chemotherapeutic Response ◽  
Non Coding Rna ◽  
Response To Chemotherapy ◽  
Personalized Oncology ◽  
Long Non Coding Rna

Genetic polymorphisms are defined as the presence of two or more different alleles in the same locus, with a frequency higher than 1% in the population. Since the discovery of long non-coding RNAs (lncRNAs), which refer to a non-coding RNA with a length of more than 200 nucleotides, their biological roles have been increasingly revealed in recent years. They regulate many cellular processes, from pluripotency to cancer. Interestingly, abnormal expression or dysfunction of lncRNAs is closely related to the occurrence of human diseases, including cancer and degenerative neurological diseases. Particularly, their polymorphisms have been found to be associated with altered drug response and/or drug toxicity in cancer treatment. However, molecular mechanisms are not yet fully elucidated, which are expected to be discovered by detailed studies of RNA–protein, RNA–DNA, and RNA–lipid interactions. In conclusion, lncRNAs polymorphisms may become biomarkers for predicting the response to chemotherapy in cancer patients. Here we review and discuss how gene polymorphisms of lncRNAs affect cancer chemotherapeutic response. This knowledge may pave the way to personalized oncology treatments.

scholarly journals DEAD-box helicases modulate dicing body formation in Arabidopsis

2021 ◽  
Vol 7 (18) ◽  
pp. eabc6266
Author(s):  
Qi Li ◽  
Ningkun Liu ◽  
Qing Liu ◽  
Xingguo Zheng ◽  
Lu Lu ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Turnip Mosaic Virus ◽  
Liquid Droplets ◽  
Phase Separations ◽  
Body Formation ◽  
Cellular Processes ◽  
Dead Box ◽  
Body Components ◽  
Liquid Phase Separations ◽  
Spatiotemporal Control

Eukaryotic cells contain numerous membraneless organelles that are made from liquid droplets of proteins and nucleic acids and that provide spatiotemporal control of various cellular processes. However, the molecular mechanisms underlying the formation and rapid stress-induced alterations of these organelles are relatively uncharacterized. Here, we investigated the roles of DEAD-box helicases in the formation and alteration of membraneless nuclear dicing bodies (D-bodies) in Arabidopsis thaliana. We uncovered that RNA helicase 6 (RH6), RH8, and RH12 are previously unidentified D-body components. These helicases interact with and promote the phase separation of SERRATE, a key component of D-bodies, and drive the formation of D-bodies through liquid-liquid phase separations (LLPSs). The accumulation of these helicases in the nuclei decreases upon Turnip mosaic virus infections, which couples with the decrease of D-bodies. Our results thus reveal the key roles of RH6, RH8, and RH12 in modulating D-body formation via LLPSs.

scholarly journals A Concerted Action of UBA5 C-Terminal Unstructured Regions Is Important for Transfer of Activated UFM1 to UFC1

2021 ◽  
Vol 22 (14) ◽  
pp. 7390
Author(s):  
Nicole Wesch ◽  
Frank Löhr ◽  
Natalia Rogova ◽  
Volker Dötsch ◽  
Vladimir V. Rogov
Keyword(s):  
Cellular Localization ◽  
Molecular Mechanisms ◽  
Biochemical Characterization ◽  
Effective Interaction ◽  
Regulatory Region ◽  
Titration Calorimetry ◽  
Enzymatic Reactions ◽  
Cellular Processes ◽  
Mechanism Of Interaction

Ubiquitin fold modifier 1 (UFM1) is a member of the ubiquitin-like protein family. UFM1 undergoes a cascade of enzymatic reactions including activation by UBA5 (E1), transfer to UFC1 (E2) and selective conjugation to a number of target proteins via UFL1 (E3) enzymes. Despite the importance of ufmylation in a variety of cellular processes and its role in the pathogenicity of many human diseases, the molecular mechanisms of the ufmylation cascade remains unclear. In this study we focused on the biophysical and biochemical characterization of the interaction between UBA5 and UFC1. We explored the hypothesis that the unstructured C-terminal region of UBA5 serves as a regulatory region, controlling cellular localization of the elements of the ufmylation cascade and effective interaction between them. We found that the last 20 residues in UBA5 are pivotal for binding to UFC1 and can accelerate the transfer of UFM1 to UFC1. We solved the structure of a complex of UFC1 and a peptide spanning the last 20 residues of UBA5 by NMR spectroscopy. This structure in combination with additional NMR titration and isothermal titration calorimetry experiments revealed the mechanism of interaction and confirmed the importance of the C-terminal unstructured region in UBA5 for the ufmylation cascade.

miR-125b enhances metastasis and progression of cancer via the TXNIP and HIF1α pathway in pancreatic cancer

2021 ◽  
pp. 1-12
Author(s):  
Pengli Wang ◽  
Dan Zheng ◽  
Hongyang Qi ◽  
Qi Gao
Keyword(s):  
Pancreatic Cancer ◽  
Hypoxia Inducible Factor ◽  
Immunofluorescence Assay ◽  
Luciferase Assay ◽  
Interacting Protein ◽  
Over Expression ◽  
Thioredoxin Interacting Protein ◽  
Cellular Processes ◽  
And Migration

BACKGROUND: MicroRNAs (miRNAs) play potential role in the development of various types of cancer conditions including pancreatic cancer (PC) targeting several cellular processes. Present study was aimed to evaluate function of miR-125b and the mechanism involved in PC. METHODS: Cell migration, MTT and BrdU study was done to establish the migration capability, cell viability and cell proliferation respectively. Binding sites for miR-125b were recognized by luciferase assay, expression of protein by western blot and immunofluorescence assay. In vivo study was done by BALB/c nude xenograft mice for evaluating the function of miR-125b. RESULTS: The study showed that expression of miR-125b was elevated in PC cells and tissues, and was correlated to proliferation and migration of cells. Also, over-expression of miR-125b encouraged migration, metastasis and proliferation of BxPC-3 cells, the suppression reversed it. We also noticed that thioredoxin-interacting protein (TXNIP) was the potential target of miR-125b. The outcomes also suggested that miR-125b governed the expression of TXNIP inversely via directly attaching to the 3′-UTR activating hypoxia-inducible factor 1α (HIF1α). Looking into the relation between HIF1α and TXNIP, we discovered that TXNIP caused the degradation and export of HIF1α by making a complex with it. CONCLUSION: The miR-125b-TXNIP-HIF1α pathway may serve useful strategy for diagnosing and treating PC.

scholarly journals Zebrafish Models of Autosomal Recessive Ataxias

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 836
Author(s):  
Ana Quelle-Regaldie ◽  
Daniel Sobrido-Cameán ◽  
Antón Barreiro-Iglesias ◽  
María Jesús Sobrido ◽  
Laura Sánchez
Keyword(s):  
Animal Models ◽  
Autosomal Recessive ◽  
Molecular Mechanisms ◽  
System Development ◽  
Rapid Development ◽  
Nervous System Development ◽  
Central Nervous System Development ◽  
Cellular Processes ◽  
Recessive Disorders

Autosomal recessive ataxias are much less well studied than autosomal dominant ataxias and there are no clearly defined systems to classify them. Autosomal recessive ataxias, which are characterized by neuronal and multisystemic features, have significant overlapping symptoms with other complex multisystemic recessive disorders. The generation of animal models of neurodegenerative disorders increases our knowledge of their cellular and molecular mechanisms and helps in the search for new therapies. Among animal models, the zebrafish, which shares 70% of its genome with humans, offer the advantages of being small in size and demonstrating rapid development, making them optimal for high throughput drug and genetic screening. Furthermore, embryo and larval transparency allows to visualize cellular processes and central nervous system development in vivo. In this review, we discuss the contributions of zebrafish models to the study of autosomal recessive ataxias characteristic phenotypes, behavior, and gene function, in addition to commenting on possible treatments found in these models. Most of the zebrafish models generated to date recapitulate the main features of recessive ataxias.

scholarly journals The Chinese Medicinal Formulation Guzhi Zengsheng Zhitongwan Modulates Chondrocyte Structure, Dynamics, and Metabolism by Controlling Multiple Functional Proteins

2018 ◽  
Vol 2018 ◽  
pp. 1-12
Author(s):  
Baojin Yao ◽  
Bocheng Lu ◽  
Mei Zhang ◽  
Hongwei Gao ◽  
Xiangyang Leng ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Research Field ◽  
Medical Systems ◽  
Cellular Processes ◽  
Structure Dynamics ◽  
National Medical ◽  
Medicinal Formulation

Traditional Chinese medicine is one of the oldest medical systems in the world and has its unique principles and theories in the prevention and treatment of human diseases, which are achieved through the interactions of different types of materia medica in the form of Chinese medicinal formulations. GZZSZTW, a classical and effective Chinese medicinal formulation, was designed and created by professor Bailing Liu who is the only national medical master professor in the clinical research field of traditional Chinese medicine and skeletal diseases. GZZSZTW has been widely used in clinical settings for several decades for the treatment of joint diseases. However, the underlying molecular mechanisms are still largely unknown. In the present study, we performed quantitative proteomic analysis to investigate the effects of GZZSZTW on mouse primary chondrocytes using state-of-the-art iTRAQ technology. We demonstrated that the Chinese medicinal formulation GZZSZTW modulates chondrocyte structure, dynamics, and metabolism by controlling multiple functional proteins that are involved in the cellular processes of DNA replication and transcription, protein synthesis and degradation, cytoskeleton dynamics, and signal transduction. Thus, this study has expanded the current knowledge of the molecular mechanism of GZZSZTW treatment on chondrocytes. It has also shed new light on possible strategies to further prevent and treat cartilage-related diseases using traditional Chinese medicinal formulations.

Structure, Function, Involvement in Diseases and Targeting of 14-3-3 Proteins: An Update

2018 ◽  
Vol 25 (1) ◽  
pp. 5-21 ◽  
Author(s):  
Ylenia Cau ◽  
Daniela Valensin ◽  
Mattia Mori ◽  
Sara Draghi ◽  
Maurizio Botta
Keyword(s):  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Physiological Role ◽  
Specific Protein ◽  
Protein Protein Interactions ◽  
Cellular Processes ◽  
Protein Partners ◽  
High Sequence Homology ◽  
Small Molecule Modulators

14-3-3 is a class of proteins able to interact with a multitude of targets by establishing protein-protein interactions (PPIs). They are usually found in all eukaryotes with a conserved secondary structure and high sequence homology among species. 14-3-3 proteins are involved in many physiological and pathological cellular processes either by triggering or interfering with the activity of specific protein partners. In the last years, the scientific community has collected many evidences on the role played by seven human 14-3-3 isoforms in cancer or neurodegenerative diseases. Indeed, these proteins regulate the molecular mechanisms associated to these diseases by interacting with (i) oncogenic and (ii) pro-apoptotic proteins and (iii) with proteins involved in Parkinson and Alzheimer diseases. The discovery of small molecule modulators of 14-3-3 PPIs could facilitate complete understanding of the physiological role of these proteins, and might offer valuable therapeutic approaches for these critical pathological states.

Desiccation-tolerance specific gene expression in leaf tissue of the resurrection plant Sporobolus stapfianus

2007 ◽  
Vol 34 (7) ◽  
pp. 589 ◽  
Author(s):  
Tuan Ngoc Le ◽  
Cecilia K. Blomstedt ◽  
Jianbo Kuang ◽  
Jennifer Tenlen ◽  
Donald F. Gaff ◽  
...  
Keyword(s):  
Drought Stress ◽  
Desiccation Tolerance ◽  
Molecular Mechanisms ◽  
Leaf Tissue ◽  
Resurrection Plant ◽  
Specific Gene ◽  
Irreversible Damage ◽  
Cellular Processes ◽  
Sporobolus Stapfianus ◽  
Normal Metabolism

The desiccation tolerant grass Sporobolus stapfianus Gandoger can modulate cellular processes to prevent the imposition of irreversible damage to cellular components by water deficit. The cellular processes conferring this ability are rapidly attenuated by increased water availability. This resurrection plant can quickly restore normal metabolism. Even after loss of more than 95% of its total water content, full rehydration and growth resumption can occur within 24 h. To study the molecular mechanisms of desiccation tolerance in S. stapfianus, a cDNA library constructed from dehydration-stressed leaf tissue, was differentially screened in a manner designed to identify genes with an adaptive role in desiccation tolerance. Further characterisation of four of the genes isolated revealed they are strongly up-regulated by severe dehydration stress and only in desiccation-tolerant tissue, with three of these genes not being expressed at detectable levels in hydrated or dehydrating desiccation-sensitive tissue. The nature of the putative proteins encoded by these genes are suggestive of molecular processes associated with protecting the plant against damage caused by desiccation and include a novel LEA-like protein, and a pore-like protein that may play an important role in peroxisome function during drought stress. A third gene product has similarity to a nuclear-localised protein implicated in chromatin remodelling. In addition, a UDPglucose glucosyltransferase gene has been identified that may play a role in controlling the bioactivity of plant hormones or secondary metabolites during drought stress.

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