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ANKRD9 is associated with tumor suppression as a substrate receptor subunit of ubiquitin ligase
Lee, Yejin,Lim, Byungho,Lee, Seon Woo,Lee, Woo Rin,Kim, Yong-In,Kim, Minhyeok,Ju, Hyoungseok,Kim, Mi Young,Kang, Suk-Jo,Song, Ji-Joon,Lee, J. Eugene,Kang, Changwon Elsevier 2018 Biochimica et biophysica acta. Molecular basis of Vol.1864 No.10
<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Human <I>ANKRD9</I> (ankyrin repeat domain 9) expression is altered in some cancers.</P> <P><B>Methods</B></P> <P>We tested genetic association of ANKRD9 with gastric cancer susceptibility and examined functional association of ANKRD9 with altered proliferation of MKN45 gastric cancer cells. We then identified ANKRD9-binding partners in HEK 293 embryonic kidney cells using quantitative proteomics, western blotting and complex reconstitution assays. We finally demonstrated ANKRD9's role of recognizing substrates for ubiquitination using in vitro ubiquitylation assay.</P> <P><B>Results</B></P> <P> <I>ANKRD9</I> is associated with cancer susceptibility in a comparison of single-nucleotide polymorphisms between 1092 gastric cancer patients and 1206 healthy controls. ANKRD9 depletion accelerates tumor progression by increasing cellular proliferation, piling up, and anchorage-independent growth of MKN45 cells. We discovered that ANKRD9 is a ubiquitin ligase substrate receptor subunit and has an anti-proliferative activity. ANKRD9 associates with CUL5 (not CUL2), ELOB, ELOC, and presumably RNF7 subunits, which together assemble into a cullin-RING superfamily E3 ligase complex. ANKRD9 belongs to the ASB family of proteins, which are characterized by the presence of ankyrin repeats and a SOCS box. In addition to its interactions with the other E3 ligase subunits, ANKRD9 interacts with two isoforms of inosine monophosphate dehydrogenase (IMPDH). These IMPDH isoforms are cognate substrates of the ANKRD9-containing E3 enzyme, which ubiquitinates them for proteasomal degradation. Their ubiquitination and turnover require the presence of ANKRD9.</P> <P><B>Conclusion</B></P> <P>ANKRD9, a previously unidentified E3 substrate receptor subunit, functions in tumor suppression by recognizing the oncoprotein IMPDH isoforms for E3 ubiquitination and proteasomal degradation.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Human <I>ANKRD9</I> is genetically associated with gastric cancer susceptibility. </LI> <LI> ANKRD9 protein activity is functionally associated with tumor suppression. </LI> <LI> ANKRD9 is a substrate receptor subunit of CUL5-based ubiquitin ligase E3 complex. </LI> <LI> E3 with ANKRD9 ubiquitinates substrate proteins for proteasomal degradation. </LI> <LI> Two isoforms of oncoprotein IMP dehydrogenase are cognate substrates of ANKRD9. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Hyoungseok Lee,Hyun Hee Cho,Il-Chan Kim,Joung Han Yim,Hong Kum Lee,Yoo Kyung Lee 한국분자세포생물학회 2008 Molecules and cells Vol.25 No.2
Deschampsia antarctica is the only monocot that thrives in the tough conditions of the Antarctic region. It is an invaluable resource for the identification of genes associated with tolerance to various environmental pressures. In order to identify genes that are differentially regulated between greenhouse-grown and Antarctic field-grown plants, we initiated a detailed gene expression analysis. Antarctic plants were collected and greenhouse plants served as controls. Two different cDNA libraries were constructed with these plants. A total of 2,112 cDNA clones was sequenced and grouped into 1,199 unigene clusters consisting of 243 consensus and 956 singleton sequences. Using similarity searches against several public databases, we constructed a functional classification of the ESTs into categories such as genes related to responses to stimuli, as well as photosynthesis and metabolism. Real-time PCR analysis of various stress responsive genes revealed different patterns of regulation in the different environments, suggesting that these genes are involved in responses to specific environmental factors.
Lee, Hyoungseok,Cho, Hyunhee,Kim, Ilchan,Yim, Jounghan,Lee, Hongkum,Lee, Yookyung Korean Society for Molecular Biology 2008 Molecules and cells Vol.25 No.2
Deschampsia antarctica is the only monocot that thrives in the tough conditions of the Antarctic region. It is an invaluable resource for the identification of genes associated with tolerance to various environmental pressures. In order to identify genes that are differentially regulated between greenhouse-grown and Antarctic field-grown plants, we initiated a detailed gene expression analysis. Antarctic plants were collected and greenhouse plants served as controls. Two different cDNA libraries were constructed with these plants. A total of 2,112 cDNA clones was sequenced and grouped into 1,199 unigene clusters consisting of 243 consensus and 956 singleton sequences. Using similarity searches against several public databases, we constructed a functional classification of the ESTs into categories such as genes related to responses to stimuli, as well as photosynthesis and metabolism. Real-time PCR analysis of various stress responsive genes revealed different patterns of regulation in the different environments, suggesting that these genes are involved in responses to specific environmental factors.
이언(Eon Lee),강형석(Hyoungseok Kang),이상석(Sangseok Lee),노상도(Sangdo Noh),이창우(KwangMyong lee),이광명(ChangWoo Lee) (사)한국CDE학회 2010 한국 CAD/CAM 학회 학술발표회 논문집 Vol.2010 No.1
Building Information Modeling (BIM) is the virtual representation of the physical and functional characteristics of a facility from inception onward. As such, it serves as a shared information repository for collaboration throughout a facility’s lifecycle. BIM is a new paradigm which can perform a diverse engineering activity such as design, simulation, structure analysis, etc and support a based information model in construction industry. In these days, many construction companies tried to perform a project efficiently by constructing and using BIM and carried out a research related in PMIS(Project Management Information System), etc. But a real case of research focused on 3D modeling object and control and share of engineering information is insufficient. In this research, we suggest an efficient BIM model and information share system based PLM for collaboration based on analyzing and researching a case of constructing BIM when perform construction project.
Expression analysis of transcripts responsive to osmotic stress in Deschampsia antarctica Desv.
Lee, Jungeun,Lee, Hyoungseok,Noh, Eun Kyeung,Park, Mira,Park, Hyun,Kim, Ji Hyun,Kim, Il-Chan,Yim, Joung Han Springer-Verlag 2014 Genes & Genomics Vol.36 No.3
Deschampsia antarctica Desv., the only monocot species thriving in the tough conditions of the Antarctic region, is surrounded by regions with snow and ice where available amount of liquid water is very limited. Considering the species as an invaluable resource for the identification of genes associated with tolerance to osmotic stress, we have characterized the physiological response and the changes in gene expression induced by PEG treatment using a cDNA macroarray. Since relative chlorophyll contents of leaves decreased to 69 %, proline levels were changed significantly, and expression levels of dehydrin and late embryogenesis abundant protein were significantly up-regulated at 1 day after PEG treatment, we used corresponding plant samples as the material for gene expression analysis. As a result of hybridization and analysis of cDNA macroarray, we identified 44 and 20 transcripts that were up-regulated and down-regulated by PEG treatment respectively, and they were divided into several functional categories. Most of the up-regulated transcripts are involved in 'Response to stimulus', 'Amino acid metabolism', and 'Respiration'. On the other hand, most of the down-regulated transcripts are involved in 'Photosynthesis' and 'Translation'. Among the up-regulated transcripts, a dagger-1-pyrroline-5-carboxylate synthase 2 gene has shown the highest expression level at 1 day after PEG treatment suggesting its possible role as a main player for proline biosynthesis in D. antarctica under osmotic stress. Collectively, these data suggest that the transcripts differentially expressed under osmotic stress may represent candidate genes for dissecting molecular mechanism of adaptation to extreme environment for plants.
Lee, Jungeun,Noh, Eun Kyeung,Choi, Hyung-Seok,Shin, Seung Chul,Park, Hyun,Lee, Hyoungseok Springer-Verlag [etc.] 2013 Planta Vol.237 No.3
<P>Antarctic hairgrass (Deschampsia antarctica Desv.) is the only natural grass species in the maritime Antarctic. It has been studied as an extremophile that has successfully adapted to marginal land with the harshest environment for terrestrial plants. However, limited genetic research has focused on this species due to the lack of genomic resources. Here, we present the first de novo assembly of its transcriptome by massive parallel sequencing and its expression profile using D. antarctica grown under various stress conditions. Total sequence reads generated by pyrosequencing were assembled into 60,765 unigenes (28,177 contigs and 32,588 singletons). A total of 29,173 unique protein-coding genes were identified based on sequence similarities to known proteins. The combined results from all three stress conditions indicated differential expression of 3,110 genes. Quantitative reverse transcription polymerase chain reaction showed that several well-known stress-responsive genes encoding late embryogenesis abundant protein, dehydrin 1, and ice recrystallization inhibition protein were induced dramatically and that genes encoding U-box-domain-containing protein, electron transfer flavoprotein-ubiquinone, and F-box-containing protein were induced by abiotic stressors in a manner conserved with other plant species. We identified more than 2,000 simple sequence repeats that can be developed as functional molecular markers. This dataset is the most comprehensive transcriptome resource currently available for D. antarctica and is therefore expected to be an important foundation for future genetic studies of grasses and extremophiles.</P>