Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 401 to 403 of 403

Publication Record


Increased drug affinity as the mechanistic basis for drug hypersensitivity of a mutant type II topoisomerase.
Froelich-Ammon SJ, Burden DA, Patchan MW, Elsea SH, Thompson RB, Osheroff N
(1995) J Biol Chem 270: 28018-21
MeSH Terms: Amino Acid Sequence, Animals, Base Sequence, Binding, Competitive, Chemokines, Cloning, Molecular, DNA Primers, Humans, Interleukin-8, Iodine Radioisotopes, Kinetics, Mice, Molecular Sequence Data, Polymerase Chain Reaction, Receptors, Interleukin, Receptors, Interleukin-8B, Recombinant Fusion Proteins, Recombinant Proteins, Sequence Homology, Amino Acid
Show Abstract · Added March 5, 2014
Altered sensitivity of topoisomerase II to anticancer drugs profoundly affects the response of eukaryotic cells to these agents. Therefore, several approaches were employed to elucidate the mechanism of drug hypersensitivity of the mutant yeast type II topoisomerase, top2H1012Y. This mutant, which is approximately 5-fold hypersensitive to ellipticine, formed DNA cleavage complexes more rapidly than the wild-type yeast enzyme in the presence of the drug. Conversely, no change in the rate of DNA religation was observed. There was, however, a correlation between increased cleavage rates and enhanced drug binding affinity. The apparent dissociation constant for ellipticine in the mutant topoisomerase II.drug.DNA ternary complex was approximately 5-fold lower than in the wild-type ternary complex. Furthermore, the apparent KD value for the mutant binary (topoisomerase II.drug) complex was approximately 2-fold lower than the corresponding wild-type complex, indicating that drug hypersensitivity is intrinsic to the enzyme. These findings strongly suggest that the enhanced ellipticine binding affinity for topoisomerase II is the mechanistic basis for drug hypersensitivity of top2H1012Y.
0 Communities
1 Members
0 Resources
19 MeSH Terms
Syk tyrosine kinase required for mouse viability and B-cell development.
Cheng AM, Rowley B, Pao W, Hayday A, Bolen JB, Pawson T
(1995) Nature 378: 303-6
MeSH Terms: Animals, B-Lymphocytes, Base Sequence, Bone Marrow Cells, Cell Differentiation, Clone Cells, DNA Primers, Enzyme Precursors, Exons, Fetal Death, Fetal Viability, Hematopoietic Stem Cell Transplantation, Hemorrhage, Humans, Intracellular Signaling Peptides and Proteins, Liver, Mice, Molecular Sequence Data, Mutagenesis, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length, Protein-Tyrosine Kinases, Receptors, Antigen, B-Cell, Signal Transduction, Syk Kinase
Show Abstract · Added March 24, 2014
The Syk cytoplasmic protein-tyrosine kinase has two amino-terminal SH2 domains and a carboxy-terminal catalytic domain. Syk, and its close relative ZAP-70, are apparently pivotal in coupling antigen- and Fc-receptors to downstream signalling events. Syk associates with activated Fc receptors, the T cell receptor complex and the B-cell antigen-receptor complex (BCR) in immature and mature B lymphocytes. On receptor activation, the tandem SH2 domains of Syk bind dual phosphotyrosine sites in the conserved ITAM motifs of receptor signalling chains, such as the immunoglobulin alpha and beta-chains of the BCR, leading to Syk activation. Here we have investigated Syk function in vivo by generating a mouse strain with a targeted mutation in the syk gene. Homozygous syk mutants suffered severe haemorrhaging as embryos and died perinatally, indicating that Syk has a critical role in maintaining vascular integrity or in wound healing during embryogenesis. Analysis of syk-/- lymphoid cells showed that the syk mutation impaired the differentiation of B-lineage cells, apparently by disrupting signalling from the pre-BCR complex and thereby preventing the clonal expansion, and further maturation, of pre-B cells.
0 Communities
1 Members
0 Resources
25 MeSH Terms
Cholesterol side-chain cleavage cytochrome P450 gene expression in the primitive gut of the mouse embryo does not require steroidogenic factor 1.
Keeney DS, Ikeda Y, Waterman MR, Parker KL
(1995) Mol Endocrinol 9: 1091-8
MeSH Terms: Animals, Base Sequence, Cholesterol Side-Chain Cleavage Enzyme, DNA Primers, DNA-Binding Proteins, Fushi Tarazu Transcription Factors, Gene Expression Regulation, Developmental, Gene Expression Regulation, Enzymologic, Homeodomain Proteins, In Situ Hybridization, Intestines, Mice, Mice, Transgenic, Molecular Sequence Data, Progesterone, RNA, Messenger, Receptors, Cytoplasmic and Nuclear, Skin, Steroidogenic Factor 1, Transcription Factors
Show Abstract · Added February 12, 2015
In situ hybridization studies reveal novel sites of expression of cholesterol side-chain cleavage cytochrome P450 (P450scc) during murine embryonic development. In addition to fetal adrenals and testes, P450scc transcripts localize in situ to the primitive gut and to a subset of unidentified cells in the dermal mesenchyme of embryonic skin. In the gut, transcripts are most abundant in luminal epithelia of the hindgut, which will form the colon. P450scc transcript abundance at these novel sites is a fraction of that in fetal adrenals or testes, suggesting a local rather than an endocrine function. Immunocytochemical analyses localize P450scc protein to the fetal hindgut, indicating that the transcripts are translated in vivo. RNA isolated from microdissected embryonic hindgut and skin was reverse transcribed and amplified by polymerase chain reaction. DNA sequence analyses of polymerase chain reaction products confirmed that specific hybridization in situ represents authentic P450scc gene (Cyp11A) transcripts and that 3 beta-hydroxysteroid dehydrogenase/delta 5-->delta 4-isomerase transcripts are also present, demonstrating the potential of these fetal tissues to produce pregnenolone and progesterone. P450scc transcripts are also detectable by in situ hybridization in primitive gut and skin of Fushi tarazu factor 1 null mice, which lack the nuclear receptor steroidogenic factor 1, proving that steroidogenic factor 1 is not required for steroid hydroxylase gene expression at these sites. The capacity for C21 steroid biosynthesis in primitive gut and skin during organogenesis raises the question whether local production of steroid hormones may be required for normal cellular growth and differentiation of these tissues during embryogenesis.
0 Communities
1 Members
0 Resources
20 MeSH Terms