TBLR1 regulates the expression of nuclear hormone receptor co-repressors

BACKGROUND: Transcription is regulated by a complex interaction of activators and repressors. The effectors of repression are large multimeric complexes which contain both the repressor proteins that bind to transcription factors and a number of co-repressors that actually mediate transcriptional silencing either by inhibiting the basal transcription machinery or by recruiting chromatin-modifying enzymes. RESULTS: TBLR1 [GenBank: NM024665] is a co-repressor of nuclear hormone transcription factors. A single highly conserved gene encodes a small family of protein molecules. Different isoforms are produced by differential exon utilization. Although the ORF of the predominant form contains only 1545 bp, the human gene occupies ~200 kb of genomic DNA on chromosome 3q and contains 16 exons. The genomic sequence overlaps with the putative DC42 [GenBank: NM030921] locus. The murine homologue is structurally similar and is also located on Chromosome 3. TBLR1 is closely related (79% homology at the mRNA level) to TBL1X and TBL1Y, which are located on Chromosomes X and Y. The expression of TBLR1 overlaps but is distinct from that of TBL1. An alternatively spliced form of TBLR1 has been demonstrated in human material and it too has an unique pattern of expression. TBLR1 and the homologous genes interact with proteins that regulate the nuclear hormone receptor family of transcription factors. In resting cells TBLR1 is primarily cytoplasmic but after perturbation the protein translocates to the nucleus. TBLR1 co-precipitates with SMRT, a co-repressor of nuclear hormone receptors, and co-precipitates in complexes immunoprecipitated by antiserum to HDAC3. Cells engineered to over express either TBLR1 or N- and C-terminal deletion variants, have elevated levels of endogenous N-CoR. Co-transfection of TBLR1 and SMRT results in increased expression of SMRT. This co-repressor undergoes ubiquitin-mediated degradation and we suggest that the stabilization of the co-repressors by TBLR1 occurs because of a novel mechanism that protects them from degradation. Transient over expression of TBLR1 produces growth arrest. CONCLUSION: TBLR1 is a multifunctional co-repressor of transcription. The structure of this family of molecules is highly conserved and closely related co-repressors have been found in all eukaryotic organisms. Regulation of co-repressor expression and the consequent alterations in transcriptional silencing play an important role in the regulation of differentiation

Deep seismic structure across the southernmost Mariana trench: Implications for arc rifting and plate hydration

Author Posting. © American Geophysical Union, 2019. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research-Solid Earth 124(5), (2019): 4710-4727, doi:10.1029/2018JB017080.The southernmost Mariana margin lacks a mature island arc and thus differs significantly from the central‐north Mariana and Izu‐Bonin margins. This paper presents a new P wave velocity model of the crust and uppermost mantle structure based on a 349‐km‐long profile of wide‐angle reflection/refraction data. The active source seismic experiment was conducted from the subducting Pacific plate to the overriding Philippine plate, passing through the Challenger Deep. The subducting plate has an average crustal thickness of ~6.0 km with Vp of 7.0 ± 0.2 km/s at the base of the crust and low values of only 5.5–6.9 km/s near the trench axis. The uppermost mantle of the subducting plate is characterized by low velocities of 7.0–7.3 km/s. The overriding plate has a maximum crustal thickness of ~18 km beneath the forearc with Vp of ~7.4 km/s at the crustal bottom and 7.5–7.8 km/s in the uppermost mantle. A zone of slight velocity reduction is imaged beneath the Southwest Mariana Rift that is undergoing active rifting. The observed significant velocity reduction in a near‐trench crustal zone of ~20–30 km in the subducting plate is interpreted as a result of faulting‐induced porosity changes and fracture‐filling fluids. The velocity reduction in the uppermost mantle of both subducting and overriding plates is interpreted as mantle serpentinization with fluid sources from dehydration of the subducting plate and/or fluid penetration along faults.Data acquisition and sample collections were supported by the Mariana Trench Initiative of the Chinese Academy of Sciences (CAS). We are grateful to the science parties and crews of R/V Shiyan 3 of the South China Sea Institute of Oceanology, CAS, for contributions to data acquisition. Constructive reviews by Robert Stern, Martha Savage, and anonymous reviewers significantly improved the manuscript. We thank Gaohua Zhu, Fan Zhang, Chunfeng Li, Zhen Sun, Zhi Wang, and Minghui Zhao for helpful discussion. The bathymetric maps were plotted using GMT (Wessel & Smith, 1995). Digital files of the velocity models and selected raw data are deposited and accessible online (at https://pan.baidu.com/s/1AbDJOgLZhYn1C‐3sg7S9Xw). This work was supported by the Strategic Priority Program of CAS (XDA13010101), CAS (Y4SL021001, QYZDY‐SSW‐DQC005, and 133244KYSB20180029), Key Laboratory of Ocean and Marginal Sea Geology, CAS (OMG18‐03), National Natural Science Foundation of China (41890813, 41676042, U1701641, 91628301, 41576041, and U1606401), and HKSAR Research Grant Council grants (14313816).2019-10-0

Recent Advances in L-Methionine Biosynthesis in Metabolically Engineered Corynebacterium glutamicum and Escherichia coli

L-Methionine is the only sulfur-containing essential amino acid. It acts as a precursor in the synthesis of various biologically active substances and participates in various metabolic pathways in the body. It is widely used in food, animal feed, medicine, cosmetics, and other fields. In recent years, since L-methionine is the only essential amino acid that cannot be industrially produced by microbial fermentation, the potential of metabolic engineering to improve L-methionine production has received widespread attention from researchers around the world. In this paper, the biosynthesis pathways and metabolic regulation mechanisms of L-methionine in Corynebacterium glutamicum and Escherichia coli are analyzed and compared. The metabolic engineering strategies to produce L-methionine are reviewed from five aspects: the removal of feedback inhibition of key enzymes, the cut-off or weakening of branch metabolic pathways, the optimization of the central metabolic regulatory network, the enhancement of cofactor supply, and the optimization of transport systems, and recent progress in research on the biosynthesis of L-methionine is summarized. Finally, future prospects are also discussed. It is hoped that this review will provide a basis for the breeding of high-yield L-methionine-producing strains

Development and validation of a prokaryotically expressed foot-and-mouth disease virus non-structural protein 2C'3AB-based immunochromatographic strip to differentiate between infected and vaccinated animals

<p>Abstract</p> <p>Background</p> <p>Foot-and-mouth disease (FMD) is an extremely contagious viral disease of cattle, pigs, sheep, goats, and many cloven-hoofed wild animals. FMDV serotypes O and Asia 1 have circulated separately in China during the last fifty years, and eliminating infected animals and vaccination are the main policies to prevent and control FMD. Antibodies to NSPs exist in infected animals, and were utilized to differentiate between infected and vaccinated animals. The reliability of detection of 3AB or 3ABC antibodies is higher than that of other NSPs. The test of 3AB is still credible because 3C protein's immunogenicity is the weakest. The 2C protein, immediately N-terminal of 3AB, was used to differentiate between infected and vaccinated animals. The use of the immunochromatographic strip is facile for clinical laboratories lacking specialized equipment and for rapid field diagnosis.</p> <p>Results</p> <p>In this study, an immunochromatographic strip with non-structural protein (NSP) 2C'3AB was developed and validated to differentiate foot-and-mouth disease infected from vaccinated animals. A part of N-terminal of 2C protein gene and whole 3AB gene were connected and prokaryotically expressed as the antigens labeled with colloidal gold was used as the detector, the 2C'3AB protein and rabbits anti-2C'3AB antibodies were blotted on the nitrocellulose(NC) membrane for the test and control lines, respectively. 387 serum samples were collected to evaluate the characteristics of the strip in comparison with existing commercial 3ABC antibody ELISA kit. The coincidence rate of pigs negative serum, pigs vaccinated serum, pigs infected serum was 100%, 97.2%, 95.0%, respectively. The coincidence rate of cattle negative serum, cattle vaccinated serum, cattle infected serum was 100%, 96.7%, 98.0%, respectively. The <b>c</b>oincidence rate of sheep negative serum, sheep infected <b>s</b>erum was 97.6%, 96.3%, respectively. The strip was shown to be of high specificity and sensitivity, good repeatability and stability.</p> <p>Conclusion</p> <p>These data suggest that the immunochromatographic strip is a useful tool for rapid on-site diagnosing animals infected foot-and-mouth disease virus.</p