A survey of expressed genes in Caenorhabditis elegans

Waterston, Robert H.; Martin, Chris; Craxton, Molly; Huynh, Chau; Coulson, Alan; Hillier, LaDeana W.; Durbin, Richard; Green, P.; Shownkeen, Ratna; Halloran, N.; Metzstein, Mark M.; Hawkins, Trevor; Wilson, Richard K.; Berks, Mary; Du, Zijin; Thomas, Karen; Thierry‐Mieg, Jean; Sulston, John

doi:10.1038/ng0592-114

Cited by 343 publications

(152 citation statements)

References 25 publications

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“…However, searching the GenBank database, we found a 463-bp and a 341-bp sequence (L11810 and L11811, respectively) corresponding to both ends of a 1.4-kb cDNA fragment isolated by a cyclic screening procedure that was used to eliminate previously identified cDNA clones from a mouse hepatic cDNA library [28]. The 341-bp sequence had an open reading frame of 113 amino acids, including the sequences matching two of the peptides obtained by trypsin digestion of the protein, V15Q and F7R (100% and 85.7% similarity, respectively) [29].…”

Section: Resultsmentioning

confidence: 99%

An adrenocorticotropin‐regulated phosphoprotein intermediary in steroid synthesis is similar to an acyl‐CoA thioesterase enzyme

Finkielstein

Maloberti

Méndez

et al. 1998

European Journal of Biochemistry

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. (1994) Eur. J. Biochem. 224, 709Ϫ716]. Here, we describe the cloning and sequencing of a cDNA encoding p43 as well as the hormonal regulation of the p43 transcript. The protein resulted homologous to a very recently described mitochondrial peroxisome-proliferator-induced very-long-chain acyl-CoA thioesterase (MTE-I). The deduced amino acid sequence of the protein shows consensus sites for phosphorylation by different protein kinases, and a lipase serine motif. Antibodies raised against a synthetic peptide that includes the lipase serine motif and against the N-terminal region of p43 block the action of the protein. The transcript of p43 was detected in ovary of pseudopregnant rats, rat adrenal zona fasciculata and glomerulosa, mouse Leydig tumor cell line (MA-10), rat brain and human placenta. Inhibition of adrenocorticotropin hormone (ACTH) release and steroid synthesis by dexamethasone produced a dose-dependent decrease in the abundance of the adrenal transcript. The transcript was induced by in vivo stimulation of the adrenals with ACTH. The effect had a rapid onset (5 min), reached maximal stimulation (62%) at 15 min, and returned to basal levels at 30 min. The effect of ACTH on the p43 transcript was inhibited by actinomycin D and enhanced by cycloheximide. Our results provide the first evidence linking acyl-CoA thioesterases with very-long-chain specificities, and a protein intermediary in steroid synthesis, thereby supporting a regulatory role for acyl-CoA thioesterases in steroidogenic tissues.

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Section: Resultsmentioning

confidence: 99%

An adrenocorticotropin‐regulated phosphoprotein intermediary in steroid synthesis is similar to an acyl‐CoA thioesterase enzyme

Finkielstein

Maloberti

Méndez

et al. 1998

European Journal of Biochemistry

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“…The high-throughput single-pass partial sequencing of cDNAs to generate ESTs has proven to be a powerful and successful way to assemble a profile of genes expressed in a particular organism, tissue, or cell type [18][19][20][22][23][24]34]. Libraries of short cDNA fragments corresponding to the 3Ј or 5Ј end regions of the mRNA have offered advantages to accelerate gene discovery and gene mapping.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Profile of Human Bone Marrow Stromal Cells: High-Throughput Expressed Sequence Tag Sequencing Analysis

et al. 2002

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Human bone marrow stromal cells (HBMSC) are pluripotent cells with the potential to differentiate into osteoblasts, chondrocytes, myelosupportive stroma, and marrow adipocytes. We used high-throughput DNA sequencing analysis to generate 4258 single-pass sequencing reactions (known as expressed sequence tags, or ESTs) obtained from the 5Ј (97) and 3Ј (4161) ends of human cDNA clones from a HBMSC cDNA library. Our goal was to obtain tag sequences from the maximum number of possible genes and to deposit them in the publicly accessible database for ESTs (dbEST of the National Center for Biotechnology Information). Comparisons of our EST sequencing data with nonredundant human mRNA and protein databases showed that the ESTs represent 1860 gene clusters. The EST sequencing data analysis showed 60 novel genes found only in this cDNA library after BLAST analysis against 3.0 million ESTs in NCBI's dbEST database. The BLAST search also showed the identified ESTs that have close homology to known genes, which suggests that these may be newly recognized members of known gene families. The gene expression profile of this cell type is revealed by analyzing both the frequency with which a message is encountered and the functional categorization of expressed sequences. Comparing an EST sequence with the human genomic sequence database enables assignment of an EST to a specific chromosomal region (a process called digital gene localization) and often enables immediate partial determination of intron/exon boundaries within the genomic structure. It is expected that high-throughput EST sequencing and data mining analysis will greatly promote our understanding of gene expression in these cells and of growth and development of the skeleton.Key Words: human bone marrow stromal cells, EST sequencing analysis, novel genes, gene expression profile, data mining them potentially useful for cell and gene therapy [2][3][4]. After extensive proliferation in vitro, the HBMSC population includes precursor cells for at least four types of connective tissue: bone, cartilage, hematopoiesis-supporting stroma, and associated adipocytes [5][6][7][8]. When single bone marrow stromal cells develop into individual HBMSC colonies, they show different morphologies and rates of proliferation. HBMSC strains derived from individual colonies also vary widely in their ability to form bone and the hematopoietic microenvironment after in vivo transplantation [9]. Despite efforts to understand the biology of HBMSC through studies 8Article doi:10.1006/geno.2001.6683, available online at http://www.idealibrary.com on IDEAL at different levels, the study of genes and proteins important to the biological phenotypes of HBMSC is still in its infancy. Well-known exceptions include STRO1 [10,11], THY1 [12,13], and SCA1 [14]. Determining the genetic expression profile of this specific cell type is key to rapid advances in understanding skeletal growth and development. The ability to peer into HBMSC and read their molecular signature will enable us to identify more preci...

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“…82 % identical with the α-isoform, although PKBγ lacks 23 amino acids at the C-terminus compared with the others [13]. Homologues have also been identified in the nematode worm Caenorhabditis elegans and the fruitfly Drosophila melanogaster, demonstrating wide evolutionary conservation [14,15].…”

Section: Cloning Of Protein Kinase B (C-akt)mentioning

confidence: 99%

“…Indeed a C. elegans PI-3K homologue has recently been implicated in mediating longevity [124]. Analysis of the role of C. elegans PKB homologues will shed light on whether this kinase mediates these survival effects [14]. A Drosophila homologue of PKB was identified by two groups [15,23].…”

Section: Genetic Analysis Of the Pkb Pathwaymentioning

confidence: 99%

Protein kinase B (c-Akt): a multifunctional mediator of phosphatidylinositol 3-kinase activation

Coffer

Jin

Woodgett

1998

Biochemical Journal

988

818

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While a plethora of extracellular molecules exist that modulate cellular functions via binding to membrane receptors inside the cell, their actions are mediated by relatively few signalling mechanisms. One of these is activation of phosphatidylinositol 3-kinase (PI-3K), which results in the generation of a membranerestricted second messenger, polyphosphatidylinositides containing a 3h-phosphate. How these molecules transduced the effects of agonists of PI-3K was unclear until the recent discovery that several protein kinases become activated upon exposure to 3h-phosphorylated inositol lipids. These enzymes include protein kinase B (PKB)\AKT and PtdIns(3,4,5)P $ -dependent kinases 1 and 2, the first two of which interact with 3h-phosphorylated ORIGINS OF AKTThe AKR strain of mice exhibit a high incidence of leukaemias and lymphomas from spontaneous thymoma [1]. A retrovirus termed AKT8 was isolated from one of these lines derived from a spontaneous thymoma. This virus was demonstrated to uniquely transform only mink lung cells (CCL64) in culture, while virus inoculated into newborn mice was shown to be tumorigenic [2]. The non-viral DNA component transduced from the mouse genome was subsequently identified, and two human homologues, AKT1 and AKT2, cloned [3]. The location of the human AKT locus was mapped to chromosome 14q32, proximal to the immunoglobulin-heavy-chain locus [4], a region frequently affected by translocations and inversions in human Tcell leukaemia\lymphoma, mixed-lineage childhood leukaemia and clonal T-cell proliferations in ataxia telangiectasia, supporting a role for this oncogene in formation of a variety of tumours [5]. Analysis of a panel of human tumours revealed a 20-fold amplification of AKT1 in a primary gastric adenocarcinoma. AKT2, on the other hand, was mapped to chromosome region 19q13.1-q13.2 and shown to be amplified and overexpressed in several ovarian carcinoma and pancreatic cancer cell lines [6,7]. A recent large-scale study of AKT2 alterations in ovarian and breast tumours revealed amplification in 12.1 % ovarian and 2.8 % breast carcinomas [8]. Furthermore, amplification of AKT2 was especially frequent in undifferentiated tumours, suggesting that AKT2 alterations may be associated with tumour aggressiveness.Abbreviations used : PI-3K, phosphatidylinositol 3-kinase ; PKB, protein kinase B ; PKA, protein kinase A ; PKC, protein kinase C ; RAC-PK, related to A-and C-kinase ; PH, pleckstrin homology ; PtdIns, phosphoinositide ; PDGF, platelet-derived growth factor ; EGF, epidermal growth factor ; bFGF, basic fibroblast growth factor ; IL, interleukin ; ERK, extracellular-signal-regulated kinase ; Btk, Bruton tyrosine kinase ; PDK, PtdIns(3,4,5)P 3 -dependent kinase ; MAPKAP, mitogen-activated protein kinase-activated protein ; SH2, Src homology 2 ; gag, group-specific antigen ; GLUT, glucose transporter ; GSK, glycogen synthase kinase ; PFK2, 6-phosphofructose-2-kinase ; IGF, insulin-like growth factor ; 4E-BP1, 4E-binding protein ; PHAS, pH-and acid-stable ; BCR-ABL, breakpoint...

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A survey of expressed genes in Caenorhabditis elegans

Cited by 343 publications

References 25 publications

An adrenocorticotropin‐regulated phosphoprotein intermediary in steroid synthesis is similar to an acyl‐CoA thioesterase enzyme

An adrenocorticotropin‐regulated phosphoprotein intermediary in steroid synthesis is similar to an acyl‐CoA thioesterase enzyme

Gene Expression Profile of Human Bone Marrow Stromal Cells: High-Throughput Expressed Sequence Tag Sequencing Analysis

Protein kinase B (c-Akt): a multifunctional mediator of phosphatidylinositol 3-kinase activation

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