Functional characterization of five novel CYP2C8 variants, G171S, R186X, R186G,
K247R, and K383N, found in a Japanese population.
AuthorsHichiya H, Tanaka-Kagawa T, Soyama A, Jinno H, Koyano S, Katori N, Matsushima E, Uchiyama S, Tokunaga H, Kimura H, Minami N, Katoh M, Sugai K, Goto Y, Tamura T, Yamamoto N, Ohe Y, Kunitoh H, Nokihara H, Yoshida T, Minami H, Saijo N, Ando M, Ozawa S, Saito Y, Sawada J,
JournalDrug Metab Dispos
PubMed ID15716363
Cytochrome P450 2C8 is one of the primary enzymes responsible for the metabolism
of a wide range of drugs such as paclitaxel, cerivastatin, and amiodarone. We have sequenced the CYP2C8
gene from 201 Japanese subjects and found five novel nonsynonymous single nucleotide polymorphisms (SNPs):
511G>A (G171S), 556C>T (R186X; X represents the translational stop ... More
Analysis of the large inactive P-TEFb complex indicates that it contains one 7SK molecule, a dimer of HEXIM1 or HEXIM2, and two P-TEFb molecules containing Cdk9 phosphorylated at threonine 186.
AuthorsLi Q, Price JP, Byers SA, Cheng D, Peng J, Price DH,
JournalJ Biol Chem
PubMed ID15965233
'Positive transcription elongation factor b (P-TEFb) regulates eukaryotic gene expression at the level of elongation, and is itself controlled by the reversible association of 7SK RNA and an RNA binding protein, HEXIM1 or HEXIM2. To further understand how P-TEFb is regulated, we analyzed the stoichiometry of all the known components ... More
HEXIM2, a HEXIM1-related protein, regulates positive transcription elongation factor b through association with 7SK.
AuthorsByers SA, Price JP, Cooper JJ, Li Q, Price DH,
JournalJ Biol Chem
PubMed ID15713662
'The kinase activity of positive transcription elongation factor b (P-TEFb), composed of cyclin-dependent kinase 9 and cyclin T1 or T2, is required for the transition of RNA polymerase II into productive elongation. P-TEFb activity has been shown to be negatively regulated by association with the small nuclear RNA 7SK and ... More
Replication-dependent destruction of Cdt1 limits DNA replication to a single round per cell cycle in Xenopus egg extracts.
AuthorsArias EE, Walter JC,
JournalGenes Dev
PubMed ID15598982
'In eukaryotes, prereplication complexes (pre-RCs) containing ORC, Cdc6, Cdt1, and MCM2-7 are assembled on chromatin in the G1 phase. In S phase, when DNA replication initiates, pre-RCs are disassembled, and new pre-RC assembly is restricted until the following G1 period. As a result, DNA replication is limited to a single ... More
Characterization of Aplysia enticin and temptin, two novel water-borne protein pheromones that act in concert with attractin to stimulate mate attraction.
'Mate attraction in Aplysia involves a long-distance water-borne signal (attractin) that is released during egg laying. Other pheromones are predicted to be released during egg laying that act in concert with albumen gland attractin to stimulate attraction, but their identities are unknown. To identify other candidate water-borne pheromones, we employed ... More
Functional analysis of three CYP1A2 variants found in a Japanese population.
AuthorsSaito Y, Hanioka N, Maekawa K, Isobe T, Tsuneto Y, Nakamura R, Soyama A, Ozawa S, Tanaka-Kagawa T, Jinno H, Narimatsu S, Sawada J,
JournalDrug Metab Dispos
PubMed ID16174806
Human cytochrome P450 1A2 (CYP1A2) catalyzes the metabolism of many important drugs and environmental chemicals. We previously reported three naturally occurring genetic polymorphisms (125C>G, Pro42Arg, CYP1A2*15; 1130G>A, Arg377Gln, *16; and 1367G>A, Arg456His, *8) found in a Japanese population. In this study, these variant enzymes were expressed in Chinese hamster V79 ... More
Competitive regulation of hepcidin mRNA by soluble and cell-associated hemojuvelin.
AuthorsLin L, Goldberg YP, Ganz T,
JournalBlood
PubMed ID15998830
Mutations in a recently identified gene HJV (also called HFE2, or repulsive guidance molecule C, RgmC) are the major cause of juvenile hemochromatosis (JH). The protein product of HJV, hemojuvelin, contains a C-terminal GPI-anchor, suggesting that it can be present in either a soluble or a cell-associated form. Patients with ... More
Human cytochrome p450 2s1: lack of activity in the metabolic activation of several cigarette smoke carcinogens and in the metabolism of nicotine.
AuthorsWang SL, He XY, Hong JY,
JournalDrug Metab Dispos
PubMed ID15608128
Cytochrome P450 (P450) enzymes play a critical role in the metabolic activation of a wide variety of environmental carcinogens. Recently, a novel human P450 enzyme, CYP2S1, has been identified. It is inducible by dioxin and other classical aryl hydrocarbon receptor ligands. However, little is known regarding the substrates and the ... More
Sox9 and p300 cooperatively regulate chromatin-mediated transcription.
AuthorsFurumatsu T, Tsuda M, Yoshida K, Taniguchi N, Ito T, Hashimoto M, Ito T, Asahara H,
JournalJ Biol Chem
PubMed ID16109717
Chromatin structure is a fundamental component of gene regulation, expression, and cellular differentiation. We have previously reported that the multifunctional coactivator p300 is a member of the Sox9-related transcriptional apparatus and activates Sox9 (Sry-type high-mobility-group box 9)-dependent transcription during chondrogenesis. However, the mechanism of synergy between Sox9 and p300 in ... More