Home About us Contact
|
Home About us Contact | ||
|
|
||
Complex Family (complex + family)
Selected AbstractsGH-secreting pituitary adenomas infrequently contain inactivating mutations of PRKAR1A and LOH of 17q23,24CLINICAL ENDOCRINOLOGY, Issue 4 2003Hiroyuki Yamasaki Summary objective The molecular events leading to the development of GH-secreting pituitary tumours remain largely unknown. Gs, (GNAS1) mutations are found in 27,43% of sporadic GH-secreting adenomas in the Caucasian population, but the frequency of GNAS1 mutations in Japanese and Korean acromegalic patients was reported to be lower, 4,9% and 16%, respectively. Other genes responsible for the tumourigenesis of GH-secreting pituitary adenomas have not been detected yet. PRKAR1A, which codes for the RI, regulatory subunit of cyclic AMP-dependent protein kinase A (PKA) on 17q23,24, was recently reported to contain inactivating mutations in some Carney complex families, which involved GH-secreting adenomas in about 10%. We re-evaluated the frequency of GNAS1 mutations and investigated PRKAR1A on the hypothesis that it might play a role in the tumourigenesis of GH-secreting adenomas. design We analysed exons 8 and 9 of GNAS1 and all exons and the exon,intron boundaries of PRKAR1A with the PCR and by direct sequencing using genomic DNA extracted from 32 GH-secreting pituitary adenomas (30 GH-secreting adenomas, two GH and PRL-secreting adenomas) and 28 corresponding peripheral blood samples, and performed loss of heterozygosity (LOH) analysis of 17q23,24 with four microsatellite markers and intragenic markers of PRKAR1A. results Seventeen of 32 (53·1%) tumours showed somatic-activating mutations of GNAS1: 16 (53·3%) of 30 GH-secreting adenomas and one of two GH and PRL-secreting adenomas. Neither inactivating somatic mutations of PRKAR1A nor LOH of 17q23,24 were detected in any of the tumours examined. conclusion We reconfirm the important role of activating mutations of GNAS1 in GH-secreting adenomas, and conclude that PRKAR1A does not play a significant role in the tumourigenesis. [source] A unique lipoylation system in the ArchaeaFEBS JOURNAL, Issue 15 2009Lipoylation in Thermoplasma acidophilum requires two proteins Members of the 2-oxoacid dehydrogenase multienzyme complex family play a key role in the pathways of central metabolism. Post-translational lipoylation of the dihydrolipoyl acyltransferase component of these complexes is essential for their activity, the lipoyllysine moiety performing the transfer of substrates and intermediates between the different active sites within these multienzyme systems. We have previously shown that the thermophilic archaeon, Thermoplasma acidophilum, has a four-gene cluster encoding the components of such a complex, which, when recombinantly expressed in Escherichia coli, can be assembled into an active multienzyme in vitro. Crucially, the E. coli host carries out the required lipoylation of the archaeal dihydrolipoyl acyltransferase component. Because active 2-oxoacid dehydrogenase multienzyme complexes have never been detected in any archaeon, the question arises as to whether Archaea possess a functional lipoylation system. In this study, we report the cloning and heterologous expression of two genes from Tp. acidophilum whose protein products together show significant sequence identity with the single lipoate protein ligase enzyme of bacteria. We demonstrate that both recombinantly expressed Tp. acidophilum proteins are required for lipoylation of the acyltransferase, and that the two proteins associate together to carry out this post-translational modification. From the published DNA sequences, we suggest the presence of functional transcriptional and translational regulatory elements, and furthermore we present preliminary evidence that lipoylation occurs in vivo in Tp. acidophilum. This is the first report of the lipoylation machinery in the Archaea, which is unique in that the catalytic activity is dependent on two separate gene products. Structured digital abstract ,,MINT-7103712: E2lipD (uniprotkb:Q9HIA5), CTD (uniprotkb:Q9HKT2) and LplA (uniprotkb:Q9HKT1) physically interact (MI:0915) by molecular sieving (MI:0071) [source] Structural organization of a complex family of palindromic repeats in EnterococciFEMS MICROBIOLOGY LETTERS, Issue 1 2009Eliana De Gregorio Abstract Enterococcus faecalis/faecium repeats (EFARs) are miniature insertion sequences spread in the genome of Enterococcus faecalis and Enterococcus faecium. Unit-length repeats measure 165,170 bp and contain two modules (B and T) capable of folding independently into stem-loop sequences, connected by a short, unstructured module J. The E. faecalis elements feature only one type of B, J and T modules. In contrast, the E. faecium elements result from the assembly of different types of B, J and T modules, and may vary in length because they carry multiple B modules. Most EFARs are located close (0,20 bp) to ORF stop codons, and are thus cotranscribed with upstream flanking genes. In both E. faecalis and E. faecium cells, EFAR transcripts accumulate in a strand-dependent fashion. Data suggest that T modules function as bidirectional transcriptional terminators, which provide a 3,-end to gene transcripts spanning B modules, while blocking antisense transcripts coming in from the opposite direction. [source] Cardiovascular pharmacology and physiology of the isoprostanesFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 5 2006Jean-Luc Cracowski Abstract F2 -isoprostanes are a complex family of compounds produced from arachidonic acid via a free radical-catalyzed mechanism. Their quantification as a pathophysiological biomarker provides a unique opportunity to investigate lipid peroxidation in vascular diseases. Their measurement also provides an interesting biomarker for the rational dose selection of antioxidants in vascular diseases where oxidative stress might be involved. In addition to their use as biomarkers, some isoprostanes possess a biological activity. The 15-series F2 - and E2 -isoprostanes mediate vasoconstriction in different vascular beds and species. In addition, 15-F2t -IsoP induces smooth muscle cells mitogenesis and monocyte adhesion to endothelial cells. The data available supports but does not prove the hypothesis that isoprostanes are involved in vascular physiology and pathogenesis. [source] Novel variants related to TT virus distributed widely in China,JOURNAL OF MEDICAL VIROLOGY, Issue 1 2002Kangxian Luo Abstract TTV is a DNA virus with high genetic heterogeneity. To investigate the novel isolates of the virus, blood samples were collected from subjects who lived in various parts of China and suffered from hepatitis or were asymptomatic carriers. Nested PCR was carried out to amplify a 3.2-kb fragment using primers deduced from the prototype TTV (TA278). The ten entire 3.2-kb nt sequences were aligned with isolate TA278, SANBAN, TUS01, and SENV retrieved from GenBank, and a phylogenetic tree was constructed by Neighbor-Joining method. The analysis indicated that five novel variants of the present study have not been described before, and all TTV-related isolates could be classified into three groups. The isolate TCHN-A, B and TUS01 were included in a group, and the remaining novel isolates together with SANBAN and TA278 clustered into another group, while SEN virus formed a distinct group. The genetic distances of the five novel variants were 0.5507,0.8476 to TA278, 0.4635,0.7877 to SANBAN, 0.6064,0.7834 to TUS01 and 0.6936,0.8236 to SENV. Of these novel variants, the ORF1 consisted of 426,772 aa and ORF2 of 141,156 aa. The nt identities of ORF1 and ORF2 between those variants and TA278, SANBAN, and TUS01 were 46.1,60.8 and 48.7,63.6%, and those of aa sequences were only 27.1,52.4 and 28.9,45.5%, respectively. The first 65 aa of ORF1 were rich in arginine and most conserved with homology of 56.5,70.0%. There was a hypervariable region from aa 286 to 403 with merely 17.7,27.0% of identity. Despite a low aa identity between TA278 and the variants, they have similar hydrophilicity profiles of ORF1. There were 2,10 N-glycosylation motifs found in these variants. In conclusion, despite the high divergence, sequences of all these isolates shared common genome organisation, ORF structure, hydrophilicity patterns, and some potential motifs with TTV prototype. It is suggested that various TTV and TTV-related isolates belong to a very large and complex family, which remains to be studied. J. Med. Virol. 67:118,126, 2002. © 2002 Wiley-Liss, Inc. [source] | |||||||||||||