Plant Mediator complex and its critical functions in transcription regulation

The Mediator complex is an important component of the eukaryotic transcriptional machinery. As an essential link between transcription factors and RNA polymerase II, the Mediator complex transduces diverse signals to genes involved in different pathways. The plant Mediator complex was recently purified and comprises conserved and specific subunits. It functions in concert with transcription factors to modulate various responses. In this review, we summarize the recent advances in understanding the plant Mediator complex and its diverse roles in plant growth, development, defense, non-coding RNA production, response to abiotic stresses, flowering, genomic stability and metabolic homeostasis. In addition, the transcription factors interacting with the Mediator complex are also highlighted.

Mediator complex components are frequent targets for genetic alterations in various types of human cancer

The Mediator co-activator complex is a highly conserved,multisubunit protein complex required for gene transcription by RNA polymerase Ⅱ（RNAPⅡ）in all eukaryotes（Allen and Taatjes,2015）.This complex,which consists of at least 30 polypeptides,can be divided into four structurally distinct sub-modules including the head,middle,tail,and cyclin-dependent kinase 8（CDK8）modules （CKM） （Fig. 1A） （Yin and Wang, 2014; Allen and Taatjes, 2015）.

Complement Protection Against Immune Complex and Acute Glomerulonephritis

in this study serum complement mediated immune complex solubilizing capacity (CMSC) and immune complement precipitation capacity (ICPIC) of 32 children with acute glomerulonephritis (AGN) were measured. The data showed that the level of serum CMSC and ICPIC was markedly decreased in acute phase and returned to normal in the 7th week after onset of disease.Correlation analysis revealed that there were positive correlation between the level of serum CMSC and ICPIC and the serum concentration of CH50, C3, C4, but no linear correlation between the level of serum CMSC and ICPIC and the amount of CIC. These results suggest that the declined serum CMSC and ICPIC in AGN may be associ ated with the pathogenesis of AGN.

Triple hit to the kidney-dual pathological crescentic glomerulonephritis and diffuse proliferative immune complexmediated glomerulonephritis: A case report

BACKGROUND Anti-glomerular basement membrane(GBM)disease is a rare rapidly progressive glomerulonephritis,frequently associated with alveolar hemorrhage in the lungs and involving the kidney by crescentic glomerulonephritis.It has been described in association with other glomerulonephritides[such as anti-neutrophilic antibody(ANCA)-glomerulonephritis,membranous nephropathy,and immunoglobulin(Ig)A nephropathy].CASE SUMMARY Herein we present an unusual case of concurrent anti-GBM disease,ANCAassociated crescentic glomerulonephritis and diffuse proliferative immune complex mediated glomerulonephritis with predominant staining for IgA and C3 by immunofluorescence.The patient is a 46-year-old Caucasian male who presented to the emergency department with acute onset of flank pain and was found to have high serum creatinine levels of 15 mg/dL,proteinuria,and hematuria.He rapidly deteriorated and became anuric.He was found to have high anti-GBM antibodies titers(151 units)and high anti-neutrophil cytoplasmic-ANCA.Despite prompt and early treatment,the patient’s condition worsened,and he succumbed to his illness.CONCLUSION Our case emphasizes the importance of a renal biopsy in anti-GBM disease,even in the presence of positive serum anti-GBM antibodies,to identify other potential causes of rapidly progressive glomerulonephritis.The challenge in treating such cases lies in the different therapy modalities.

Barrier stabilizing mediators in regulation of microvascular endothelial permeability

Increase of microvascular permeability is one of the most important pathological events in the pathogenesis of trauma and burn injury. Massive leakage of fluid from vascular space leads to lose of blood plasma and decrease of effective circulatory blood volume, result- ing in formation of severe tissue edema, hypotension or even shock, especially in severe burn injury. Fluid resusci- tation has been the only valid approach to sustain patient＇s blood volume for a long time, due to the lack of overall and profound understanding of the mechanisms of vascular hyperpermeability response. There is an emerging concept in recent years that some so-called barrier stabilizing media- tors play a positive role in preventing the increase ofvascu-lar permeability. These mediators may be released in re- sponse to proinflammatory mediators and serve to restore endothelial barrier function. Some of these stabilizing mediators are important even in quiescent state because they preserve basal vascular permeability at low levels. This review introduces some of these mediators and reveals their underlying signaling mechanisms during endothelial barrier enhancing process.

Sorting and Processing of the Alzheimer's Disease Amyloid Precursor Protein Mediated by the AP-4 Complex

Proteolytic processing of the transmembrane amyloid precursor protein (APP) to aggregation-prone amyloid-β (Aβ) peptide underlies the development of Alzheimer’s disease.

Dysregulation of CDK8 and Cyclin C in tumorigenesis

Appropriately controlled gene expression is fundamental for normal growth and survival of all living organisms. In eukaryotes, the tran- scription of protein-coding mRNAs is dependent on RNA polymerase II （Pol II）. The multi-subunit transcription cofactor Mediator complex is proposed to regulate most, if not all, of the Pol II-dependent transcription. Here we focus our discussion on two subunits of the Mediator complex, cyclin-dependent kinase 8 （CDK8） and its regulatory partner Cyclin C （CycC）, because they are either mutated or amplified in a variety of human cancers. CDK8 functions as an oncoprotein in melanoma and colorectal cancers, thus there are considerable interests in developing drugs specifically targeting the CDK8 kinase activity. However, to evaluate the feasibility of targeting CDK8 for cancer therapy and to understand how their dysregulation contributes to tumorigenesis, it is essential to elucidate the in vivo function and regulation of CDKS-CycC, which are still poorly understood in multi-cellular organisms. We summarize the evidence linking their dysregulation to various cancers and present our bioinformatics and computational analyses on the structure and evolution of CDK8. We also discuss the implications of these observations in tumorigenesis. Because most of the Mediator subunits, including CDK8 and CycC, are highly conserved during eukaryotic evolution, we expect that investigations using model organisms such as Drosophila will provide important insights into the function and regulation of CDK8 and CycC in different cellular and developmental contexts.

Mutation of MED12 is not a frequent occurrence in prostate cancer of Korean patients

Prostate cancer is one of the major health care problems, but the molecular pathogenesis has been relatively insufficiently elucidated. Recently, whole exome sequencing of prostate cancer identified recurrent mutations involving MED12 in Caucasian patients, which finding was not reproduced in one subsequent study by Sanger sequencing. Thus, we investigated mutation status of MED12 in exons 2 and 26 by Sanger sequencing in 102 radical prostatectomy cases from Korean patients. The analysis found the mutation in none of the cases. Therefore, MED12 mutation does not appear to represent a significant molecular alteration in this cohort of patients according to the analysis by the traditional ＂gold standard.＂

Hsa-miR-637 inhibits human hepatocyte proliferation by targeting Med1-interacting proteins

Background:Recent studies have shown that mediator complex subunit 1(Med1)can significantly affect hepatocyte proliferation and differentiation.Acting as a tumor suppressor,microRNA-637(hsa-miR-637)can inhibit the growth of hepatocarcinoma cells and further induce cell apoptosis.However,the function of hsa-miR-637 and its target genes during liver regeneration remains to be elucidated.Methods:This study used co-immunoprecipitation(Co-IP)assay,transfection,luciferase reporter assay,functional assay by cell counting kit-8(CCK-8),Annexin V-FITC/propidium iodide apoptosis assay,and quantitative polymerase chain reaction analysis of chromatin immunoprecipitation(ChIP)for analysis.Results:Hsa-miR-637 has been suggested to suppress the expression of two Med1-interacting nuclear receptors,identified as the peroxisome proliferator-activated receptor alpha(PPARA)and thyroid hormone receptor alpha(THRA)at the transcriptional and translational levels in the human liver HL-7702 cell line.The interaction between Med1 and PPARA/THRA in HL-7702 cells was then confirmed.The transcriptional repression of hsa-miR-637 on PPARA and THRA was also demonstrated.Moreover,hsamiR-637 has been determined to suppress the proliferation of HL-7702 cells.Furthermore,cell cycle arrest of HL-7702 cells was induced by transfection of hsa-miR-637 at the S phase,but its apoptosis failed.Finally,PPARA was indicated to directly bind to the promoter of some transcription factors,like bcatenin,mouse double minute 2(MDM2),and p53.Conclusions:This study has confirmed that hsa-miR-637 plays an antiproliferative role during liver regeneration,which may contribute in understanding the regenerative process of the liver.

Molar Mass Dispersity Control by lodine-mediated Reversibledeactivation Radical Polymerization

Dispersity(D)of polymers has a great effect on the properties of polymeric materials,and therefore how to control θ is very important but still a huge challenge in polymer synthesis,especially for reversible-deactivation radical polymerization(RDRP)strategy.Herein,we successfully developed a novel strategy to adjust D of polymers by visible light-controlled reversible complexation mediated living radical polymerizatio n(RCMP)and combi nation of single-electron transfer-degenerative chain tran sfer living radical polymerization(SET-DTLRP)at room temperature.In RCMP system,2-iodo-2-methylpropionitrile(CP-I)and ethyl 2-iodo-2-phenylacetate(EIPA)were used as alkyl iodide initiators,by using methyl methacrylate(MMA)as the model monomer and n-butylacrylate(BA)as the end-capping reagent to regulate D of polymers.Subsequently,we successfully prepared the block copolymer PMMA-b-PBA with adjustable D by reactivating the polymer end-chains via SET-DTLRP in the presence of copper wire,fully dem on strati ng that it is a promising strategy that can keep the"living"feature of polymers while regulating their molar mass dispersities easily.