AID-induced decrease in topoisomerase 1 induces DNA structural alteration and DNA cleavage for class switch recombination.
AuthorsKobayashi M, Aida M, Nagaoka H, Begum NA, Kitawaki Y, Nakata M, Stanlie A, Doi T, Kato L, Okazaki IM, Shinkura R, Muramatsu M, Kinoshita K, Honjo T,
JournalProc Natl Acad Sci U S A
PubMed ID20018730
'To initiate class switch recombination (CSR) activation-induced cytidine deaminase (AID) induces staggered nick cleavage in the S region, which lies 5'' to each Ig constant region gene and is rich in palindromic sequences. Topoisomerase 1 (Top1) controls the supercoiling of DNA by nicking, rotating, and religating one strand of DNA. ... More
Identification of protein targets of 4-hydroxynonenal using click chemistry for ex vivo biotinylation of azido and alkynyl derivatives.
AuthorsVila A, Tallman KA, Jacobs AT, Liebler DC, Porter NA, Marnett LJ,
JournalChem Res Toxicol
PubMed ID18232660
'Polyunsaturated fatty acids (PUFA) are primary targets of free radical damage during oxidative stress. Diffusible electrophilic alpha,beta-unsaturated aldehydes, such as 4-hydroxynonenal (HNE), have been shown to modify proteins that mediate cell signaling (e.g., IKK and Keap1) and alter gene expression pathways responsible for inducing antioxidant genes, heat shock proteins, and ... More
A concomitant loss of dormant origins and FANCC exacerbates genome instability by impairing DNA replication fork progression.
AuthorsLuebben SW, Kawabata T, Johnson CS, O'Sullivan MG, Shima N,
Journal
PubMed ID24589582
'Accumulating evidence suggests that dormant DNA replication origins play an important role in the recovery of stalled forks. However, their functional interactions with other fork recovery mechanisms have not been tested. We previously reported intrinsic activation of the Fanconi anemia (FA) pathway in a tumor-prone mouse model (Mcm4(chaos3)) with a ... More
Metabolic labeling of sialic acids in living animals with alkynyl sugars.
AuthorsChang PV, Chen X, Smyrniotis C, Xenakis A, Hu T, Bertozzi CR, Wu P,
JournalAngew Chem Int Ed Engl
PubMed ID19388017
Sialome sweet sialome: As sialic acids are involved in many host-pathogen recognition events and are markers of embryonic and malignant tissues, there is great interest in methods for the enrichment and identification of sialylated glycoproteins from complex tissues. Now N-(4-pentynoyl)mannosamine can be used to metabolically label sialylated glycoproteins in living ... More
Regulation of the Skeletal Muscle Ryanodine Receptor/Ca2+-release Channel RyR1 by S-Palmitoylation.
AuthorsChaube R, Hess DT, Wang YJ, Plummer B, Sun QA, Laurita K, Stamler JS,
Journal
PubMed ID24509862
The ryanodine receptor/Ca(2+)-release channels (RyRs) of skeletal and cardiac muscle are essential for Ca(2+) release from the sarcoplasmic reticulum that mediates excitation-contraction coupling. It has been shown that RyR activity is regulated by dynamic post-translational modifications of Cys residues, in particular S-nitrosylation and S-oxidation. Here we show that the predominant ... More
Pyrethroid activity-based probes for profiling cytochrome P450 activities associated with insecticide interactions.
AuthorsIsmail HM, O'Neill PM, Hong DW, Finn RD, Henderson CJ, Wright AT, Cravatt BF, Hemingway J, Paine MJ,
Journal
PubMed ID24248381
Pyrethroid insecticides are used to control diseases spread by arthropods. We have developed a suite of pyrethroid mimetic activity-based probes (PyABPs) to selectively label and identify P450s associated with pyrethroid metabolism. The probes were screened against pyrethroid-metabolizing and nonmetabolizing mosquito P450s, as well as rodent microsomes, to measure labeling specificity, ... More
Targeting of the MNK-eIF4E axis in blast crisis chronic myeloid leukemia inhibits leukemia stem cell function.
AuthorsLim S, Saw TY, Zhang M, Janes MR, Nacro K, Hill J, Lim AQ, Chang CT, Fruman DA, Rizzieri DA, Tan SY, Fan H, Chuah CT, Ong ST,
Journal
PubMed ID23737503
Chronic myeloid leukemia responds well to therapy targeting the oncogenic fusion protein BCR-ABL1 in chronic phase, but is resistant to treatment after it progresses to blast crisis (BC). BC is characterized by elevated ß-catenin signaling in granulocyte macrophage progenitors (GMPs), which enables this population to function as leukemia stem cells ... More
Approach to profile proteins that recognize post-translationally modified histone
AuthorsLi X, Kapoor TM,
JournalJ Am Chem Soc
PubMed ID20141135
Post-translational modifications (PTMs) of histones, proteins onto which DNA is packaged, are involved in many biological processes, including transcription, recombination, and chromosome segregation. As these PTMs can be dynamic, combinatorial, and mediators of weak interactions, the comprehensive profiling of all proteins that recognize histone PTMs is a daunting task. Here ... More
Imaging the lipidome: omega-alkynyl fatty acids for detection and cellular visualization of lipid-modified proteins.
AuthorsHannoush RN, Arenas-Ramirez N,
JournalACS Chem Biol
PubMed ID19505150
Fatty acylation or lipid modification of proteins controls their cellular activation and diverse roles in physiology. It mediates protein-protein and protein-membrane interactions and plays an important role in regulating cellular signaling pathways. Currently, there is need for visualizing lipid modifications of proteins in cells. Herein we report novel chemical probes ... More
Reversibility of covalent electrophile-protein adducts and chemical toxicity.
AuthorsLin D, Saleh S, Liebler DC,
JournalChem Res Toxicol
PubMed ID19548357
The biotin-tagged electrophiles 1-biotinamido-4-(4'-[maleimidoethylcyclohexane]-carboxamido)butane (BMCC) and N-iodoacetyl-N-biotinylhexylenediamine (IAB) have been used as model electrophile probes in complex proteomes to identify protein targets associated with chemical toxicity. Whereas IAB activates stress signaling and apoptosis in HEK293 cells, BMCC does not. Cysteine Michael adducts formed from BMCC and nonbiotinylated analogues rapidly disappeared ... More
Robust fluorescent detection of protein fatty-acylation with chemical reporters.
AuthorsCharron G, Zhang MM, Yount JS, Wilson J, Raghavan AS, Shamir E, Hang HC,
JournalJ Am Chem Soc
PubMed ID19281244
Fatty-acylation of proteins in eukaryotes is associated with many fundamental cellular processes but has been challenging to study due to limited tools for rapid and robust detection of protein fatty-acylation in cells. The development of azido-fatty acids enabled the nonradioactive detection of fatty-acylated proteins in mammalian cells using the Staudinger ... More
Alkynyl sugar analogs for the labeling and visualization of glycoconjugates in cells.
AuthorsHsu TL, Hanson SR, Kishikawa K, Wang SK, Sawa M, Wong CH
JournalProc Natl Acad Sci U S A
PubMed ID17296930
Developing tools for investigating the cellular activity of glycans will help to delineate the molecular basis for aberrant glycosylation in pathological processes such as cancer. Metabolic oligosaccharide engineering, which inserts sugar-reporting groups into cellular glycoconjugates, represents a powerful method for imaging the localization, trafficking, and dynamics of glycans and isolating ... More