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Post translational modification

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https://www.readbyqxmd.com/read/29443976/how-many-human-proteoforms-are-there
#1
Ruedi Aebersold, Jeffrey N Agar, I Jonathan Amster, Mark S Baker, Carolyn R Bertozzi, Emily S Boja, Catherine E Costello, Benjamin F Cravatt, Catherine Fenselau, Benjamin A Garcia, Ying Ge, Jeremy Gunawardena, Ronald C Hendrickson, Paul J Hergenrother, Christian G Huber, Alexander R Ivanov, Ole N Jensen, Michael C Jewett, Neil L Kelleher, Laura L Kiessling, Nevan J Krogan, Martin R Larsen, Joseph A Loo, Rachel R Ogorzalek Loo, Emma Lundberg, Michael J MacCoss, Parag Mallick, Vamsi K Mootha, Milan Mrksich, Tom W Muir, Steven M Patrie, James J Pesavento, Sharon J Pitteri, Henry Rodriguez, Alan Saghatelian, Wendy Sandoval, Hartmut Schlüter, Salvatore Sechi, Sarah A Slavoff, Lloyd M Smith, Michael P Snyder, Paul M Thomas, Mathias Uhlén, Jennifer E Van Eyk, Marc Vidal, David R Walt, Forest M White, Evan R Williams, Therese Wohlschlager, Vicki H Wysocki, Nathan A Yates, Nicolas L Young, Bing Zhang
Despite decades of accumulated knowledge about proteins and their post-translational modifications (PTMs), numerous questions remain regarding their molecular composition and biological function. One of the most fundamental queries is the extent to which the combinations of DNA-, RNA- and PTM-level variations explode the complexity of the human proteome. Here, we outline what we know from current databases and measurement strategies including mass spectrometry-based proteomics. In doing so, we examine prevailing notions about the number of modifications displayed on human proteins and how they combine to generate the protein diversity underlying health and disease...
February 14, 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/29443975/features-and-regulation-of-non-enzymatic-post-translational-modifications
#2
REVIEW
Robert Harmel, Dorothea Fiedler
Non-enzymatic post-translational modifications of proteins can occur when a nucleophilic or redox-sensitive amino acid side chain encounters a reactive metabolite. In many cases, the biological function of these modifications is limited by their irreversibility, and consequently these non-enzymatic modifications are often considered as indicators of stress and disease. Certain non-enzymatic post-translational modifications, however, can be reversed, which provides an additional layer of regulation and renders these modifications suitable for controlling a diverse set of cellular processes ranging from signaling to metabolism...
February 14, 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/29443041/in-vitro-sumoylation-assay-to-study-sumo-e3-ligase-activity
#3
Wan-Shan Yang, Mel Campbell, Hsing-Jien Kung, Pei-Ching Chang
Small ubiquitin-like modifier (SUMO) modification is an important post-translational modification (PTM) that mediates signal transduction primarily through modulating protein-protein interactions. Similar to ubiquitin modification, SUMOylation is directed by a sequential enzyme cascade including E1-activating enzyme (SAE1/SAE2), E2-conjugation enzyme (Ubc9), and E3-ligase (i.e., PIAS family, RanBP2, and Pc2). However, different from ubiquitination, an E3 ligase is non-essential for the reaction but does provide precision and efficacy for SUMO conjugation...
January 29, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29442498/proteostasis-and-the-regulation-of-intra-and-extracellular-protein-aggregation-by-atp-independent-molecular-chaperones-lens-%C3%AE-crystallins-and-milk-caseins
#4
John A Carver, Heath Ecroyd, Roger J W Truscott, David C Thorn, Carl Holt
Molecular chaperone proteins perform a diversity of roles inside and outside the cell. One of the most important is the stabilization of misfolding proteins to prevent their aggregation, a process that is potentially detrimental to cell viability. Diseases such as Alzheimer's, Parkinson's, and cataract are characterized by the accumulation of protein aggregates. In vivo, many proteins are metastable and therefore under mild destabilizing conditions have an inherent tendency to misfold, aggregate, and hence lose functionality...
February 14, 2018: Accounts of Chemical Research
https://www.readbyqxmd.com/read/29440318/monitoring-the-5-methoxycarbonylmethyl-2-thiouridine-mcm5s2u-modification-in-eukaryotic-trnas-via-the-gamma-toxin-endonuclease
#5
Jenna M Lentini, Jillian Ramos, Dragony Fu
The post-transcriptional modification of tRNA at the wobble position is a universal process occurring in all domains of life. In eukaryotes, the wobble uridine of particular tRNAs is transformed to the 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U) modification which is critical for proper mRNA decoding and protein translation. However, current methods to detect mcm5s2U are technically challenging and/or require specialized instrumental expertise. Here, we show that gamma-toxin endonuclease from the yeast Kluyveromyces lactis can be used as a probe for assaying mcm5s2U status in the tRNA of diverse eukaryotic organisms ranging from protozoans to mammalian cells...
February 13, 2018: RNA
https://www.readbyqxmd.com/read/29438997/doxorubicin-induced-dna-damage-causes-extensive-ubiquitination-of-ribosomal-proteins-associated-with-a-decrease-in-protein-translation
#6
Vincentius A Halim, Iraia García-Santisteban, Daniel O Warmerdam, Bram van den Broek, Albert J R Heck, Shabaz Mohammed, René H Medema
Protein post-translational modifications (PTMs) play a central role in the DNA damage response. In particular, protein phosphorylation and ubiquitination have been shown to be essential in the signalling cascade that coordinates break repair with cell cycle progression. Here, we performed whole-cell quantitative proteomics to identify global changes in protein ubiquitination that are induced by DNA double-strand breaks. In total, we quantified more than 9400 ubiquitin sites and found that the relative abundance of approximately 10% of these sites was altered in response to DNA double-strand breaks...
February 8, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29434080/exploring-peptide-hormones-in-plants-identification-of-four-peptide-hormone-receptor-pairs-and-two-post-translational-modification-enzymes
#7
Yoshikatsu Matsubayashi
The identification of hormones and their receptors in multicellular organisms is one of the most exciting research areas and has lead to breakthroughs in understanding how their growth and development are regulated. In particular, peptide hormones offer advantages as cell-to-cell signals in that they can be synthesized rapidly and have the greatest diversity in their structure and function. Peptides often undergo post-translational modifications and proteolytic processing to generate small oligopeptide hormones...
2018: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
https://www.readbyqxmd.com/read/29433191/enhanced-arginine-biosynthesis-and-lower-proteolytic-profile-as-indicators-of-saccharomyces-cerevisiae-stress-in-stationary-phase-during-fermentation-of-high-sugar-grape-must-a-proteomic-evidence
#8
Olta Noti, Enrico Vaudano, Maria Gabriella Giuffrida, Cristina Lamberti, Laura Cavallarin, Emilia Garcia-Moruno, Enrica Pessione
A strain of Saccharomyces (S) cerevisiae (ISE19), which displayed an initial good adaptation to a high sugar medium with increased acetate and glycerol production but weak overall growth/fermentation performances, was selected during the alcoholic fermentation of Cortese grape must. To obtain insights into the metabolic changes that occur in the must during growth in particular conditions (high ethanol, high residual sugars and low nitrogen availability) leading to a sluggish fermentation or even fermentation arrest, comparative in-gel proteomic analyses were performed on cells grown in media containing 200g/L and 260g/L of glucose, respectively, while the YAN (Yeast Assimilable Nitrogen) concentration was maintained as it was...
March 2018: Food Research International
https://www.readbyqxmd.com/read/29432431/improving-succinylation-prediction-accuracy-by-incorporating-the-secondary-structure-via-helix-strand-and-coil-and-evolutionary-information-from-profile-bigrams
#9
Abdollah Dehzangi, Yosvany López, Sunil Pranit Lal, Ghazaleh Taherzadeh, Abdul Sattar, Tatsuhiko Tsunoda, Alok Sharma
Post-translational modification refers to the biological mechanism involved in the enzymatic modification of proteins after being translated in the ribosome. This mechanism comprises a wide range of structural modifications, which bring dramatic variations to the biological function of proteins. One of the recently discovered modifications is succinylation. Although succinylation can be detected through mass spectrometry, its current experimental detection turns out to be a timely process unable to meet the exponential growth of sequenced proteins...
2018: PloS One
https://www.readbyqxmd.com/read/29432143/protein-phosphatases-at-the-nuclear-envelope
#10
REVIEW
Raquel Sales Gil, Ines J de Castro, Jerusalem Berihun, Paola Vagnarelli
The nuclear envelope (NE) is a unique topological structure formed by lipid membranes (Inner and Outer Membrane: IM and OM) interrupted by open channels (Nuclear Pore complexes). Besides its well-established structural role in providing a physical separation between the genome and the cytoplasm and regulating the exchanges between the two cellular compartments, it has become quite evident in recent years that the NE also represents a hub for localized signal transduction. Mechanical, stress, or mitogen signals reach the nucleus and trigger the activation of several pathways, many effectors of which are processed at the NE...
February 6, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/29432007/functional-role-and-hierarchy-of-the-intermolecular-interactions-in-binding-of-protein-kinase-clients-to-the-hsp90-cdc37-chaperone-structure-based-network-modeling-of-allosteric-regulation
#11
Gabrielle Stetz, Gennady M Verkhivker
A fundamental role of the Hsp90-Cdc37 chaperone machinery in mediating conformational development and activation of diverse protein kinase clients is essential for signal transduction. Structural and biochemical studies have demonstrated that characterization of global conformational changes and allosteric interactions in the Hsp90-Cdc37-kinase complexes are central to our understanding of the mechanisms underlying kinase recruitment and processing by the Hsp90-Cdc37 chaperone. The recent cryo-electron microscopy structure of the Hsp90-Cdc37-Cdk4 kinase complex has provided a framework for dissecting regulatory principles underlying differentiation and recruitment of protein kinase clients to the chaperone machinery...
February 12, 2018: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29431050/tdp-43-post-translational-modifications-in-health-and-disease
#12
Emanuele Buratti
Nuclear factor TDP-43 is a ubiquitously expressed RNA binding protein that plays a key causative role in several neurodegenerative diseases, especially in the ALS/FTD spectrum. In addition, its aberrant aggregation and expression has been recently observed in other type of diseases, such as myopathies and Niemann-Pick C, a lysosomal storage disease. Areas Covered. This review aims to specifically cover the post-translational modifications (PTMs) that can affect TDP-43 function and cellular status both in health and disease...
February 10, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29430559/developmental-lead-and-or-prenatal-stress-exposures-followed-by-different-types-of-behavioral-experience-result-in-the-divergence-of-brain-epigenetic-profiles-in-a-sex-brain-region-and-time-dependent-manner-implications-for-neurotoxicology
#13
Deborah A Cory-Slechta, Marissa Sobolewski, G Varma, J S Schneider
Over a lifetime, early developmental exposures to neurocognitive risk factors, such as lead (Pb) exposures and prenatal stress (PS), will be followed by multiple varied behavioral experiences. Pb, PS and behavioral experience can each influence brain epigenetic profiles. Our recent studies show a greater level of complexity, however, as all three factors interact within each sex to generate differential adult variation in global post-translational histone modifications (PTHMs), which may result in fundamentally different consequences for life-long learning and behavioral function...
October 2017: Current Opinion in Toxicology
https://www.readbyqxmd.com/read/29428128/role-of-forkhead-box-o-foxo-transcription-factor-in-aging-and-diseases
#14
REVIEW
Neelam Tia, Alok Kumar Singh, Poorti Pandey, Chandra Shekhar Azad, Pritee Chaudhary, Indrajeet Singh Gambhir
Fork head box O (FOXO) transcription factor is a key player in an evolutionarily conserved pathway. The mammalian FOXO family consists of FOXO1, 3, 4 and 6, are highly similar in their structure, function and regulation. To maintain optimum body function, the organisms have developed complex mechanisms for homeostasis. Importantly, it is well known that when these mechanisms dysregulate it results in the development of age-related disease. FOXO proteins are involved in a diverse cellular function and also have clinical significance including cell cycle arrest, cell differentiation, tumour suppression, DNA repair, longevity, diabetic complications, immunity, wound healing, regulation of metabolism and thus treatment of several types of diseases...
March 30, 2018: Gene
https://www.readbyqxmd.com/read/29427667/o-glcnacylation-modulates-pka-creb-signaling-in-a-manner-specific-to-pka-catalytic-subunit-isoforms
#15
Nana Jin, Denglei Ma, Jianlan Gu, Jianhua Shi, Xiaotao Xu, Khalid Iqbal, Cheng-Xin Gong, Fei Liu, Dandan Chu
O-GlcNAcylation is a post-translational modification of proteins. Protein kinase A (PKA)-cAMP response element binding protein (CREB) signaling plays critical roles in multiple biological processes. Isoforms α and β of PKA catalytic subunit (PKAc) and CREB are modified by O-GlcNAcylation. In the present study, we determined the role of O-GlcNAcylation in PKAc isoform-specific CREB signaling. We found that up-regulation of O-GlcNAcylation enhanced CREB phosphorylation, but suppressed CREB expression in exogenous PKAc isoform-unspecific manner...
February 7, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29427113/molecular-mechanisms-and-cellular-pathways-implicated-in-machado-joseph-disease-pathogenesis
#16
Clévio Nóbrega, Ana Teresa Simões, Joana Duarte-Neves, Sónia Duarte, Ana Vasconcelos-Ferreira, Janete Cunha-Santos, Dina Pereira, Magda Santana, Cláudia Cavadas, Luís Pereira de Almeida
Machado-Joseph disease (MJD) is a dominantly inherited disorder originally described in people of Portuguese descent, and associated with the expansion of a CAG tract in the coding region of the causative gene MJD1/ATX3. The CAG repeats range from 10 to 51 in the normal population and from 55 to 87 in SCA3/MJD patients. MJD1 encodes ataxin-3, a protein whose physiological function has been linked to ubiquitin-mediated proteolysis. Despite the identification of the causative mutation, the pathogenic process leading to the neurodegeneration observed in the disease is not yet completely understood...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29427109/polyglutamine-independent-features-in-ataxin-3-aggregation-and-pathogenesis-of-machado-joseph-disease
#17
Ana Luisa Carvalho, Alexandra Silva, Sandra Macedo-Ribeiro
The expansion of a trinucleotide (CAG) repeat, translated into a polyglutamine expanded sequence in the protein encoded by the MJD gene, was identified over 20 years ago as the causative mutation in a severe neurodegenerative disorder originally diagnosed in individuals of Portuguese ancestry. This incapacitating disease, called Machado-Joseph disease or spinocebellar ataxia type 3, is integrated into a larger group of neurodegenerative disorders-the polyglutamine expansion disorders-caused by extension of a CAG repeat in the coding sequence of otherwise unrelated genes...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29427101/spinocerebellar-ataxia-type-1-molecular-mechanisms-of-neurodegeneration-and-preclinical-studies
#18
Judit M Pérez Ortiz, Harry T Orr
Spinocerebellar ataxia type 1 (SCA1) is an adult-onset, inherited disease that leads to degeneration of Purkinje cells of the cerebellum and culminates in death 10-30 years after disease onset. SCA1 is caused by a CAG repeat mutation in the ATXN1 gene, encoding the ATXN1 protein with an abnormally expanded polyglutamine tract. As neurodegeneration progresses, other brain regions become involved and contribute to cognitive deficits as well as problems with speech, swallowing, and control of breathing. The fundamental basis of pathology is an aberration in the normal function of Purkinje cells affecting regulation of gene transcription and RNA splicing...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29427100/x-linked-spinal-and-bulbar-muscular-atrophy-from-clinical-genetic-features-and-molecular-pathology-to-mechanisms-underlying-disease-toxicity
#19
Constanza J Cortes, Albert R La Spada
Spinal and Bulbar Muscular Atrophy (SBMA) is an inherited neuromuscular disorder caused by a CAG-polyglutamine (polyQ) repeat expansion in the androgen receptor (AR) gene. Unlike other polyQ diseases, where the function of the native causative protein is unknown, the biology of AR is well understood, and this knowledge has informed our understanding of how native AR function interfaces with polyQ-AR dysfunction. Furthermore, ligand-dependent activation of AR has been linked to SBMA disease pathogenesis, and has led to a thorough study of androgen-mediated effects on polyQ-AR stability, degradation, and post-translational modifications, as well as their roles in the disease process...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29427077/post-translational-regulation-of-the-maternal-to-zygotic-transition
#20
REVIEW
Chao Liu, Yanjie Ma, Yongliang Shang, Ran Huo, Wei Li
The maternal-to-zygotic transition (MZT) is essential for the developmental control handed from maternal products to newly synthesized zygotic genome in the earliest stages of embryogenesis, including maternal component (mRNAs and proteins) degradation and zygotic genome activation (ZGA). Various protein post-translational modifications have been identified during the MZT, such as phosphorylation, methylation and ubiquitination. Precise post-translational regulation mechanisms are essential for the timely transition of early embryonic development...
February 9, 2018: Cellular and Molecular Life Sciences: CMLS
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