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Post translational modifications

Mark Hedglin, Binod Pandey, Stephen J Benkovic
Translesion DNA synthesis (TLS) during S-phase uses specialized TLS DNA polymerases to replicate a DNA lesion, allowing stringent DNA synthesis to resume beyond the offending damage. Human TLS involves the conjugation of ubiquitin to PCNA clamps encircling damaged DNA and the role of this post-translational modification is under scrutiny. A widely-accepted model purports that ubiquitinated PCNA recruits TLS polymerases such as pol η to sites of DNA damage where they may also displace a blocked replicative polymerase...
October 22, 2016: ELife
Akhi Akhter, Emanuel Rosonina
The Saccharomyces cerevisiae transcription factor Gcn4 is expressed during amino acid starvation and its abundance is controlled by ubiquitin-mediated proteolysis. Cdk8, a kinase component of the RNA polymerase II Mediator complex, phosphorylates Gcn4 which triggers its ubiquitination/proteolysis and is thought to link Gcn4 degradation with transcription of target genes. In addition to phosphorylation and ubiquitination, we previously showed that Gcn4 becomes sumoylated in a DNA-binding dependent manner, while a non-sumoylatable form of Gcn4 showed increased chromatin occupancy, but only if Cdk8 was present...
October 21, 2016: Genetics
Liqing Wang, Suresh Kumar, Satinder Dahiya, Feng Wang, Jian Wu, Kheng Newick, Rongxiang Han, Arabinda Samanta, Ulf H Beier, Tatiana Akimova, Tricia R Bhatti, Benjamin Nicholson, Mathew P Kodrasov, Saket Agarwal, David E Sterner, Wei Gu, Joseph Weinstock, Tauseef R Butt, Steven M Albelda, Wayne W Hancock
Foxp3+ T-regulatory (Treg) cells are known to suppress protective host immune responses to a wide variety of solid tumors, but their therapeutic targeting is largely restricted to their transient depletion or "secondary" modulation, e.g. using anti-CTLA-4 monoclonal antibody. Our ongoing studies of the post-translational modifications that regulate Foxp3 demonstrated that the histone/protein acetyltransferase, Tip60, plays a dominant role in promoting acetylation, dimerization and function in Treg cells. We now show that the ubiquitin-specific protease, Usp7, controls Treg function largely by stabilizing the expression and promoting the multimerization of Tip60 and Foxp3...
October 15, 2016: EBioMedicine
Srikanth Appikonda, Kaushik N Thakkar, Michelle Craig Barton
Tripartite Motif-containing protein 24 (TRIM24) functions as an E3 ligase targeting p53 for ubiquitination, a histone 'reader' that interacts with a specific signature of histone post-translational modifications and a co-regulator of nuclear receptor-regulated transcription. Although mouse models of Trim24 depletion suggest that TRIM24 may be a liver-specific tumor suppressor, several studies show that human TRIM24 is an oncogene when aberrantly over expressed. This review focuses on the mechanisms of TRIM24 functions in oncogenesis and metabolic reprogramming, which underlie recent interest in therapeutic targeting of aberrant TRIM24 in human cancers...
March 2016: Drug Discovery Today. Technologies
Yuxin Shu, Yan Lu, Xiaojuan Pang, Wei Zheng, Yahong Huang, Jiahong Li, Jianguo Ji, Can Zhang, Pingping Shen
Peroxisome proliferator-activating receptor γ (PPARγ), a transcription factor, is involved in many important biological processes, including cell terminal differentiation, survival and apoptosis. However, the role of PPARγ, which regulates tumour promoter and oncogene expression, is not well understood in hepatocellular carcinoma (HCC). In the present study, based on evidence from clinical samples that phosphorylation of PPARγ at Ser84 is up-regulated in human liver tumours, we confirmed that phosphorylation of PPARγ was also significantly increased in an HCC mouse model and was increased by Mitogen-activated protein kinase (MEK)/ Extracellular-signal-regulated kinases (ERK) kinase...
October 19, 2016: Oncotarget
Junting Huang, Gerald W Zamponi
Calcium entry via voltage gated calcium channels mediates a wide range of physiological functions, whereas calcium channel dysregulation has been associated with numerous pathophysiological conditions. There are myriad cell signaling pathways that act on voltage gated calcium channels to fine tune their activities and to regulate their cell surface expression. These regulatory mechanisms include the activation of G protein-coupled receptors and downstream phosphorylation events, and their control over calcium channel trafficking through direct physical interactions...
October 18, 2016: Current Opinion in Pharmacology
Shobini Jayaraman, Jose Luis Sánchez-Quesada, Olga Gursky
Lipids in the body are transported via lipoproteins that are nanoparticles comprised of lipids and amphipathic proteins termed apolipoproteins. This family of lipid surface-binding proteins is over-represented in human amyloid diseases. In particular, all major proteins of high-density lipoproteins (HDL), including apoA-I, apoA-II and serum amyloid A, can cause systemic amyloidoses in humans upon protein mutations, post-translational modifications or overproduction. Here, we begin to explore how the HDL lipid composition influences amyloid deposition by apoA-I and related proteins...
October 18, 2016: Biochimica et Biophysica Acta
Michelle R Robinson, Jennifer S Brodbelt
Tyrosine sulfation is an important post-translational modification but remains difficult to detect in biological samples owing to its low stoichiometric abundance and the lack of effective enrichment methods. In the present study, weak anion exchange (WAX) is evaluated for the enrichment of sulfopeptides that have been modified via carbamylation to convert all primary amines to less basic carbamates. The decrease in basicity enhanced the binding of carbamylated sulfopeptides to WAX resin relative to non-sulfated peptides...
October 21, 2016: Analytical Chemistry
Wenqi Yang, Wei Zhang, Xiaoxue Wang
The plant phytohormone abscisic acid (ABA) plays significant roles in integrating environmental signals with embryogenesis, germination, seedling establishment, the floral transition, and the adaptation of plants to stressful environments by modulating stomatal movement and stress-responsive gene expression. ABA signaling consists of ABA perception, signal transduction, and ABA-induced responses. ABA receptors such as members of the PYR/PYL family, group A type 2C protein phosphatases (as negative regulators), SnRK2 protein kinases (as positive regulators), bZIP transcription factors, and ion channels are key components of ABA signaling...
October 21, 2016: Plant Biotechnology Journal
Wannapa Sornjai, Pathrapol Lithanatudom, Jenny Erales, Philippe Joly, Alain Francina, Sabine Hacot, Suthat Fucharoen, Saovaros Svasti, Jean Jacques Diaz, Hichem C Mertani, Duncan R Smith
Ribosome biogenesis is the process of synthesis of the cellular ribosomes which mediate protein translation. Integral with the ribosomes are four cytoplasmic ribosomal RNAs (rRNAs) which show extensive post-transcriptional modifications including 2'-O-methylation and pseudouridylation. Several hereditary hematologic diseases including Diamond-Blackfan anemia have been shown to be associated with defects in ribosome biogenesis. Thalassemia is the most important hematologic inherited genetic disease worldwide, and this study examined the post-transcriptional ribose methylation status of three specific active sites of the 28S rRNA molecule at positions 1858, 4197 and 4506 of β-thalassemia trait carriers and normal controls...
October 17, 2016: International Journal of Biological Macromolecules
Manuela Antonioli, Martina Di Rienzo, Mauro Piacentini, Gian Maria Fimia
Autophagy is a major degradative process activated in a rapid and transient manner to cope with stress conditions. Whether autophagy is beneficial or detrimental depends upon the rate of induction and the appropriateness of the duration. Alterations in both autophagy initiation and termination predispose the cell to death, and affect the execution of other inducible processes such as inflammation. In this review we discuss how stress signaling pathways dynamically control the activity of the autophagy machinery by mediating post-translational modifications and regulatory protein interactions...
October 17, 2016: Trends in Biochemical Sciences
J Z Zhao, X Q Zheng, M Gao
Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a lipid and protein phosphatase that functions as a tumor suppressor. PTEN regulates the multiple biological processes such as cell proliferation, invasion, metastasis, apoptosis and stem cell self-renewal through the phosphatidylinositol 3-kinase/ protein kinase B signaling pathway. PTEN activity can be modulated by mutations, epigenetic silencing, transcriptional repression, post-transcriptional contral and post-translational modifications.
October 7, 2016: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke za Zhi, Chinese Journal of Otorhinolaryngology Head and Neck Surgery
Inderjeet Kaur, Mohammad Zeeshan, Ekta Saini, Abhinav Kaushik, Asif Mohmmed, Dinesh Gupta, Pawan Malhotra
Post-transcriptional and post-translational modifications play a major role in Plasmodium life cycle regulation. Lysine methylation of histone proteins is well documented in several organisms, however in recent years lysine methylation of proteins outside histone code is emerging out as an important post-translational modification (PTM). In the present study we have performed global analysis of lysine methylation of proteins in asexual blood stages of Plasmodium falciparum development. We immunoprecipitated stage specific Plasmodium lysates using anti-methyl lysine specific antibodies that immunostained the asexual blood stage parasites...
October 20, 2016: Scientific Reports
Takeshi Harada, Hideki Yamamoto, Shosei Kishida, Michiko Kishida, Chihiro Awada, Toshifumi Takao, Akira Kikuchi
Wnt5b, a member of the same family of proteins as Wnt5a of which overexpression is associated with cancer aggressiveness, is suggested to be involved in cancer progression, however details remain unclarified. We analyzed biochemical properties of purified Wnt5b and the mode of secretion of Wnt5b by cancer cells. Wnt5b was glycosylated at three asparagine residues and lipidated at one serine residue, and these post-translational modifications of Wnt5b are essential for secretion. Purified Wnt5b showed Dvl2 phosphorylation and Rac activation abilities to a similar extent as Wnt5a...
October 20, 2016: Cancer Science
Bin Cai, Xiangxiong Kong, Chao Zhong, Suli Sun, Xiao Feng Zhou, Yin Hua Jin, Youning Wang, Xia Li, Zhendong Zhu, Jing Bo Jin
SIZ1 is a small ubiquitin-related modifier (SUMO) E3 ligase that mediates post-translational SUMO modification of target proteins and thereby regulates developmental processes and hormonal and environmental stress responses in Arabidopsis. However, the role of SUMO E3 ligases in crop plants is largely unknown. Here, we identified and characterized two Glycine max (soybean) SUMO E3 ligases, GmSIZ1a and GmSIZ1b. Expression of GmSIZ1a and GmSIZ1b was induced in response to salicylic acid (SA), heat, and dehydration treatment, but not in response to cold, ABA, and NaCl treatment...
October 20, 2016: Journal of Integrative Plant Biology
Jing Jiao, Rongxiang Han, Wayne W Hancock, Ulf H Beier
Determining protein acetylation by immunoprecipitation and immunoblotting can be challenging, especially if the tissue of interest is low in quantity, and when good quality acetylation site-specific antibodies are not available. Proximity ligation assays allow a sensitive and quantitative method to assess Foxp3 acetylation in regulatory T cells, with as little as 1.5 × 10(5) cells within two days turnaround time. This method is of potential use in other similar scenarios, when post-translational modifications of a protein of interest need to be determined with only a small amount of sample and in the absence of specific antibodies that can assess the post-translational modification in the protein of interest...
2017: Methods in Molecular Biology
Florian Hoss, Juan F Rodriguez-Alcazar, Eicke Latz
The inflammasome adapter ASC links activated inflammasome sensors to the effector molecule pro-caspase-1. Recruitment of pro-caspase-1 to ASC promotes the autocatalytic activation of caspase-1, which leads to the release of pro-inflammatory cytokines, such as IL-1β. Upon triggering of inflammasome sensors, ASC assembles into large helical fibrils that interact with each other serving as a supramolecular signaling platform termed the ASC speck. Alternative splicing, post-translational modifications of ASC, as well as interaction with other proteins can perturb ASC function...
October 19, 2016: Cellular and Molecular Life Sciences: CMLS
Eva Liñeiro, Cristina Chiva, Jesús M Cantoral, Eduard Sabido, Francisco Javier Fernández-Acero
Phosphorylation is one of the main post-translational modification (PTM) involved in signaling network in the ascomycete Botrytis cinerea, one of the most relevant phytopathogenic fungus. The data presented in this article provided a differential mass spectrometry-based analysis of the phosphoproteome of B. cinerea under two different phenotypical conditions induced by the use of two different elicitors: glucose and deproteinized Tomate Cell Walls (TCW). A total 1138 and 733 phosphoproteins were identified for glucose and TCW culture conditions respectively...
June 2016: Data in Brief
Caiyun He, Guori Gao, Jianguo Zhang, Aiguo Duan, Hongmei Luo
BACKGROUND: Low temperature is one of the crucial environmental factors limiting the productivity and distribution of plants. Sea buckthorn (Hippophae rhamnoides L.), a well recognized multipurpose plant species, live successfully in in cold desert regions. But their molecular mechanisms underlying cold tolerance are not well understood. METHODS: Physiological and biochemical responses to low-temperature stress were studied in seedlings of sea buckthorn. Differentially expressed protein spots were analyzed using multiplexing fluorescent two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with matrix-assisted laser desorption/ionization (MALDI) time-of-flight/time-of-flight (TOF/TOF) mass spectrometry (MS), the concentration of phytohormone was measured using enzyme-linked immunosorbent assay, and a spectrophotometric assay was used to measure enzymatic reactions...
2016: Proteome Science
Wei-Lin Wang, David Shechter
Chromatin, primarily a complex of DNA and histone proteins, is the physiological form of the genome. Chromatin is generally repressive for transcription and other information transactions that occur on DNA. A wealth of post-translational modifications on canonical histones and histone variants encode regulatory information to recruit or repel effector proteins on chromatin, promoting and further repressing transcription and thereby form the basis of epigenetic information. During metazoan oogenesis, large quantities of histone proteins are synthesized and stored in preparation for the rapid early cell cycles of development and to elicit maternal control of chromatin assembly pathways...
2016: International Journal of Developmental Biology
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