St. Jude Children's Research Hospital

About: St. Jude Children's Research Hospital is a healthcare organization based out in Memphis, Tennessee, United States. It is known for research contribution in the topics: Population & Virus. The organization has 9344 authors who have published 19233 publications receiving 1233399 citations. The organization is also known as: St. Jude Children's Hospital & St. Jude Hospital.

P-glycoprotein: a major determinant of rifampicin-inducible expression of cytochrome P4503A in mice and humans

Abstract: The P-glycoprotein (Pgp) efflux pump can influence the hepatocellular concentration of xenobiotics that are modulators and substrates of cytochrome P4503A (CYP3A). We tested the hypothesis that Pgp is a determinant of drug-inducible expression of CYP3A. The magnitude of CYP3A induction by rifampicin was compared in the human parental colon carcinoma cell line LS 180/WT (wild type) and in two derivative clones overexpressing the human multidrug resistance gene MDR1 (also designated PGY1) because of either drug selection (LS 180/ADR) or transfection with MDRI cDNA (LS 180/MDR). In both MDR1 cDNA-overexpressing clones, rifampicin induction of CYP3A mRNA and protein was decreased and required greater rifampicin concentrations compared with parental cells. The role of Pgp in regulation of CYP3A expression in vivo was analyzed in mice carrying a targeted disruption of the mdr1a mouse gene. Oral treatment with increasing doses of rifampicin resulted in elevated drug levels in the livers of mdr1a (-/-) mice compared with mdr1a (+/+) mice at all doses. Consistent with the enhanced accumulation of rifampicin in mdr1a (-/-) mice, lower doses of rifampicin were required for induction of CYP3A proteins, and the magnitude of CYP3A induction was greater at all doses of rifampicin in mdr1a (-/-) mice compared with mdr1a (+/+) mice. We conclude that Pgp-mediated transport is a critical element influencing the CYP3A inductive response.

Fusion of the Leucine Zipper Gene HLF to the E2A Gene in Human Acute B-Lineage Leukemia

Abstract: A t(17;19) chromosomal translocation in early B-lineage acute leukemia was shown to result in chimeric transcripts that contain sequences from the E2A basic helix-loop-helix transcription factor gene on chromosome 19, fused to sequences from a previously unidentified gene (HLF) on chromosome 17 that encodes a hepatic leukemia factor. The chimeric protein consisted of the amino-terminal transactivation domain of E2A linked to the carboxyl-terminal basic region-leucine zipper domain of HLF. HLF was normally expressed in liver and kidney, but not in lymphoid cells, and was found to be closely related to the leucine zipper-containing transcription factors DBP (albumin D-box binding protein) and TEF (thyrotroph embryonic factor), which regulate developmental stage-specific gene expression.

Cell surface molecule associated with lymphocyte homing is a ubiquitinated branched-chain glycoprotein

Abstract: Partial amino acid sequence analysis of a purified lymphocyte homing receptor demonstrates the presence of two amino termini, one of which corresponds precisely to the amino terminus of ubiquitin. This observation extends the province of this conserved polypeptide to the cell surface and leads to a proposed model of the receptor complex as a core polypeptide modified by glycosylation and ubiquitination. Independent antibodies to ubiquitin serve to identify additional cell surface species, an indication that ubiquitination of cell surface proteins may be more general. It is proposed that functional binding of lymphocytes to lymph node high endothelial venules might involve the ubiquitinated region of the receptor; if true, cell surface ubiquitin could play a more general role in cell-cell interaction and adhesion.