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1.
ChiWei Yeh WeiChieh Huang PangHung Hsu KunHai Yeh LiChin Wang Paul WeiChe Hsu HsiuChuan Lin YiNing Chen ShuChuan Chen ChenHsiang Yeang HsuehChi S Yen 《The EMBO journal》2021,40(7)
Protein termini are determinants of protein stability. Proteins bearing degradation signals, or degrons, at their amino‐ or carboxyl‐termini are eliminated by the N‐ or C‐degron pathways, respectively. We aimed to elucidate the function of C‐degron pathways and to unveil how normal proteomes are exempt from C‐degron pathway‐mediated destruction. Our data reveal that C‐degron pathways remove mislocalized cellular proteins and cleavage products of deubiquitinating enzymes. Furthermore, the C‐degron and N‐degron pathways cooperate in protein removal. Proteome analysis revealed a shortfall in normal proteins targeted by C‐degron pathways, but not of defective proteins, suggesting proteolysis‐based immunity as a constraint for protein evolution/selection. Our work highlights the importance of protein termini for protein quality surveillance, and the relationship between the functional proteome and protein degradation pathways. 相似文献
2.
Daria Grafodatskaya Barian HY Chung Darci T Butcher Andrei L Turinsky Sarah J Goodman Sana Choufani Yi-An Chen Youliang Lou Chunhua Zhao Rageen Rajendram Fatima E Abidi Cindy Skinner James Stavropoulos Carolyn A Bondy Jill Hamilton Shoshana Wodak Stephen W Scherer Charles E Schwartz Rosanna Weksberg 《BMC medical genomics》2013,6(1):1-18
Background
A number of neurodevelopmental syndromes are caused by mutations in genes encoding proteins that normally function in epigenetic regulation. Identification of epigenetic alterations occurring in these disorders could shed light on molecular pathways relevant to neurodevelopment.Results
Using a genome-wide approach, we identified genes with significant loss of DNA methylation in blood of males with intellectual disability and mutations in the X-linked KDM5C gene, encoding a histone H3 lysine 4 demethylase, in comparison to age/sex matched controls. Loss of DNA methylation in such individuals is consistent with known interactions between DNA methylation and H3 lysine 4 methylation. Further, loss of DNA methylation at the promoters of the three top candidate genes FBXL5, SCMH1, CACYBP was not observed in more than 900 population controls. We also found that DNA methylation at these three genes in blood correlated with dosage of KDM5C and its Y-linked homologue KDM5D. In addition, parallel sex-specific DNA methylation profiles in brain samples from control males and females were observed at FBXL5 and CACYBP.Conclusions
We have, for the first time, identified epigenetic alterations in patient samples carrying a mutation in a gene involved in the regulation of histone modifications. These data support the concept that DNA methylation and H3 lysine 4 methylation are functionally interdependent. The data provide new insights into the molecular pathogenesis of intellectual disability. Further, our data suggest that some DNA methylation marks identified in blood can serve as biomarkers of epigenetic status in the brain. 相似文献3.
P. Arokiaraj H. Yeet Yeang K. Fong Cheong S. Hamzah H. Jones S. Coomber B. V. Charlwood 《Plant cell reports》1998,17(8):621-625
Hevea brasiliensis anther calli were genetically transformed using Agrobacterium GV2260 (p35SGUSINT) that harboured the β-glucuronidase (gus) and neomycin phosphotransferase (nptII) genes. β-Glucuronidase protein (GUS) was expressed in the leaves of kanamycin-resistant plants that were regnerated, and the presence
of the gene was confirmed by Southern analysis. GUS was also observed to be expressed in the latex and more importantly in
the serum fraction. Transverse sections of the leaf petiole from a transformed plant revealed GUS expression to be especially
enhanced in the phloem and laticifers. GUS expression was subsequently detected in every one of 194 plants representing three
successive vegetative cycles propagated from the original transformant. Transgenic Hevea could thus facilitate the continual production of foreign proteins expressed in the latex.
Received: 14 February 1997 / Revision received: 16 August 1997 / Accepted: 20 July 1997 相似文献
4.
Yeang Chen-Hsiang; Darot Jeremy F. J.; Noller Harry F.; Haussler David 《Molecular biology and evolution》2007,24(10):2354
Mol. Biol. Evol. 24: 1592–1595. 2007. doi:10.1093/molbev/msm142 The following corrections were not incorporated into the paper: 1) In 相似文献
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A probabilistic graphical model is proposed in order to detect the coevolution between different sites in biological sequences. The model extends the continuous-time Markov process of sequence substitution for single nucleic or amino acids and imposes general constraints regarding simultaneous changes on the substitution rate matrix. Given a multiple sequence alignment for each molecule of interest and a phylogenetic tree, the model can predict potential interactions within or between nucleic acids and proteins. Initial validation of the model is carried out using tRNA and 16S rRNA sequence data. The model accurately identifies the secondary interactions of tRNA as well as several known tertiary interactions. In addition, results on 16S rRNA data indicate this general and simple coevolutionary model outperforms several other parametric and nonparametric methods in predicting secondary interactions. Furthermore, the majority of the putative predictions exhibit either direct contact or proximity of the nucleotide pairs in the 3-dimensional structure of the Thermus thermophilus ribosomal small subunit. The results on RNA data suggest a general model of coevolution might be applied to other types of interactions between protein, DNA, and RNA molecules. 相似文献
7.
Validation and refinement of gene-regulatory pathways on a network of physical interactions 总被引:1,自引:0,他引:1
As genome-scale measurements lead to increasingly complex models of gene regulation, systematic approaches are needed to validate and refine these models. Towards this goal, we describe an automated procedure for prioritizing genetic perturbations in order to discriminate optimally between alternative models of a gene-regulatory network. Using this procedure, we evaluate 38 candidate regulatory networks in yeast and perform four high-priority gene knockout experiments. The refined networks support previously unknown regulatory mechanisms downstream of SOK2 and SWI4. 相似文献
8.
Arif SA Hamilton RG Yusof F Chew NP Loke YH Nimkar S Beintema JJ Yeang HY 《The Journal of biological chemistry》2004,279(23):23933-23941
9.
Abstract: The fossil record of the callianassid genus Glypturus (Decapoda, Axiidea) is re‐evaluated. Our systematic revision, both of extant and fossil taxa, is based on major cheliped morphology only, thus providing an important impetus for palaeontological studies. Both spination and tuberculation of chelipeds are herein considered of great taxonomic importance. Presence of spines on the upper margins of the merus and propodus and the lower margin of the carpus are significant for generic assignment, whereas the extent of tuberculation on lateral surfaces of the propodus is important for assignment at the species level. Altogether, four extant and six exclusively fossil species of Glypturus are recognized. Several extinct callianassid taxa are now transferred to the genus, namely Callianassa berryi, Callianassa fraasi, Callianassa munieri, Callianassa pugnax and Callianassaspinosa; Callianassa pseudofraasi is considered a junior synonym of C. fraasi. Based on a comparison of ecological preferences of extant representatives, the presence of Glypturus in the fossil record is considered to be linked with tropical to subtropical, nearshore carbonate environments of normal salinity. We argue that Glypturus is of Tethyan origin, with a stratigraphical range going as far back as the Eocene. Since then, the genus migrated both westwards and eastwards, establishing present‐day communities in the western Atlantic and Indo‐West Pacific which both comprise several distinct species. In the presumed area of origin, the genus does no longer occur today. The exlusively fossil (middle Eocene) genus Eoglypturus from Italy is considered closely related to Glypturus and is thus assigned to the subfamily Callichirinae as well. 相似文献
10.
Yeang C Varshney S Wang R Zhang Y Ye D Jiang XC 《Biochimica et biophysica acta》2008,1781(10):610-617
Sphingomyelin synthase (SMS) sits at the crossroads of sphingomyelin (SM), ceramide, diacylglycerol (DAG) metabolism. It utilizes ceramide and phosphatidylcholine as substrates to produce SM and DAG, thereby regulating lipid messengers which play a role in cell survival and apoptosis. There are two isoforms of the enzyme, SMS1 and SMS2. Both SMS1 and SMS2 contain two histidines and one aspartic acid which are evolutionary conserved within the lipid phosphate phosphatase superfamily. In this study, we systematically mutated these amino acids using site-directed mutagenesis and found that each point mutation abolished SMS activity without altering cellular distribution. We also explored the domains which are responsible for cellular distribution of both enzymes. Given their role as a potential regulator of diseases, these findings, coupled with homology modeling of SMS1 and SMS2, will be useful for drug development targeting SMS. 相似文献