The effect of estrogen-mediated ubiquitin on cardiovascular diseases:a bioinformatics analysis

Objective:Using data mining tools,study the potential pathways of estrogen’s cardiovascular effects.Methods:The GeneExpression Omnibus database was used to download the relevant high-throughput microarray dataset GSE72180,which was then analyzed for differential genes using the GEO2R online analysis tool,gene function and pathway enrichment analysis using DAVID 6.8,protein interaction network analysis using the STRING database,and core network extraction using the MCODE algorithm.Results:A total of 131 differential genes were identified and enriched for gene function and signaling pathway analysis,which indicated that these genes were related with focal adhesion and the HIF-1 signaling pathway.MCODE algorithm analysis extracted 1 core sub-network of these genes to be related to ubiquitin protein transferase activity,protein polyubiquitination,protein ubiquitination involved in ubiquitin-dependent proteolytic metabolic processes,ligase activity,and clustering on ubiquitin-mediated protein hydrolysis signaling pathway.Conclusion:By using data mining tools,it is possible to identify how estrogen may influence the cardiovascular system by controlling the ubiquitination process.This information may be used as a reference for etiology and preventive studies of cardiovascular illnesses.

Modification of ubiquitin C-terminal hydrolase L1 by reactive lipid species: role in neural regeneration and diseases of aging

Role of ubiquitin C-terminal hydrolase L1（UCHL1）in brain function：Ubiquitin is used by a variety of cellular systems to tag proteins for transport to various organelles.There are a number of enzymes in the ubiquitin-proteasome pathway（UPP）that tag abnormally folded proteins with ubiquitin for transport to the proteasome for degradation.

Ferricyanide-Promoted Oxidative Activation and Ligation of Protein Thioacids in Neutral Aqueous Media

Ferricyanide-promoted oxidative activation of Nacylatedα-aminothioacids for amide bond formation withα-aminonitriles was recently shown to be a plausible pathway for prebiotic peptide synthesis.Herein we describe the finding that by adding sodium azide and thiols,ferricyanide oxidation can elicit highly efficient and clean conversion of fully unprotected peptide or protein thioacids in neutral aqueous media to the corresponding thioesters.This transformation enables the development of ferricyanide-promoted thioacid-based native chemical ligation(NCL)as a new redox-based method for chemical protein synthesis,which does not need to change pH and is therefore operationally easy for ligation at small scales.The effectiveness of the ferricyanide-promoted thioacid-based NCL was illustrated by synthesis of an ISG15-modified MDA5 segment under nondenaturing conditions and synthesis of an acetylated ubiquitin(Ub)-modified histone H2A through an N-to-C sequential ligation.This work broadens the concept of on-demand oxidative activation strategy for protein ligation and provides a new useful supplement to the repertoire of methods for chemical protein synthesis,particularly for studies on proteins carrying Ub family modifications.

PLMD：An updated data resource of protein lysine modifications

Post-translational modifications（PTMs） occurring at protein lysine residues,or protein lysine modifications（PLMs）,play critical roles in regulating biological processes.Due to the explosive expansion of the amount of PLM substrates and the discovery of novel PLM types,here we greatly updated our previous studies,and presented a much more integrative resource of protein lysine modification database（PLMD）.In PLMD,we totally collected and integrated 284,780 modification events in 53,501 proteins across 176 eukaryotes and prokaryotes for up to 20 types of PLMs,including ubiquitination, acetylation, sumoylation, methylation ,succinylation,malonylation,glutarylation,giycation,formylation,hydroxylation,butyrylation,propionylation,crotonylation,pupylation,neddylation,2-hydroxyisobutyrylation,phosphoglycerylation,carboxylation,lipoylation and biotinylation.Using the data set,a motif-based analysis was performed for each PLM type,and the results demonstrated that different PLM types preferentially recognize distinct sequence motifs for the modifications.Moreover,various PLMs synergistically orchestrate specific cellular biological processes by mutual crosstalks with each other,and we totally found 65,297 PLM events involved in 90 types of PLM co-occurrences on the same lysine residues.Finally,various options were provided for accessing the data,while original references and other annotations were also present for each PLM substrate.Taken together,we anticipated the PLMD database can serve as a useful resource for further researches of PLMs.PLMD 3.0 was implemented in PHP ＋ MySQL and freely available at http：//plmd.biocuckoo.org.