Chang C

References (14)

Title : Cofactorless oxygenases guide anthraquinone-fused enediyne biosynthesis - Gui_2023_Nat.Chem.Biol__
Author(s) : Gui C , Kalkreuter E , Liu YC , Li G , Steele AD , Yang D , Chang C , Shen B
Ref : Nat Chemical Biology , : , 2023
Abstract : The anthraquinone-fused enediynes (AFEs) combine an anthraquinone moiety and a ten-membered enediyne core capable of generating a cytotoxic diradical species. AFE cyclization is triggered by opening the F-ring epoxide, which is also the site of the most structural diversity. Previous studies of tiancimycin A, a heavily modified AFE, have revealed a cryptic aldehyde blocking installation of the epoxide, and no unassigned oxidases could be predicted within the tnm biosynthetic gene cluster. Here we identify two consecutively acting cofactorless oxygenases derived from methyltransferase and alpha/beta-hydrolase protein folds, TnmJ and TnmK2, respectively, that are responsible for F-ring tailoring in tiancimycin biosynthesis by comparative genomics. Further biochemical and structural characterizations reveal that the electron-rich AFE anthraquinone moiety assists in catalyzing deformylation, epoxidation and oxidative ring cleavage without exogenous cofactors. These enzymes therefore fill important knowledge gaps for the biosynthesis of this class of molecules and the underappreciated family of cofactorless oxygenases.
ESTHER : Gui_2023_Nat.Chem.Biol__
PubMedSearch : Gui_2023_Nat.Chem.Biol__
PubMedID: 37945897
Gene_locus related to this paper: strsp-TnmK2

Title : Intramolecular C-C Bond Formation Links Anthraquinone and Enediyne Scaffolds in Tiancimycin Biosynthesis - Gui_2022_J.Am.Chem.Soc__
Author(s) : Gui C , Kalkreuter E , Liu YC , Adhikari A , Teijaro CN , Yang D , Chang C , Shen B
Ref : Journal of the American Chemical Society , : , 2022
Abstract : First discovered in 1989, the anthraquinone-fused enediynes are a class of DNA-cleaving bacterial natural products composed of a DNA-intercalating anthraquinone moiety and a 10-membered enediyne warhead. However, until recently, there has been a lack of genetically amenable hosts and sequenced biosynthetic gene clusters available for solving the biosynthetic questions surrounding these molecules. Herein, we have identified and biochemically and structurally characterized TnmK1, a member of the alpha/beta-hydrolase fold superfamily responsible for the C-C bond formation linking the anthraquinone moiety and enediyne core together in tiancimycin (TNM) biosynthesis. In doing so, two intermediates, TNM H and TNM I, in anthraquinone-fused enediyne biosynthesis, containing an unprecedented cryptic C16 aldehyde group, were identified. This aldehyde plays a key role in the TnmK1-catalyzed C-C bond formation via a Michael addition, representing the first example of this chemistry for the alpha/beta-hydrolase fold superfamily. Additionally, TNM I shows sub-nanomolar cytotoxicity against selected cancer cell lines, indicating a new mechanism of action compared to previously known anthraquinone-fused enediynes. Together, the findings from this study are expected to impact enzymology, natural product biosynthesis, and future efforts at enediyne discovery and drug development.
ESTHER : Gui_2022_J.Am.Chem.Soc__
PubMedSearch : Gui_2022_J.Am.Chem.Soc__
PubMedID: 36279548
Gene_locus related to this paper: strsp-TnmK1

Title : The Chara Genome: Secondary Complexity and Implications for Plant Terrestrialization - Nishiyama_2018_Cell_174_448
Author(s) : Nishiyama T , Sakayama H , de Vries J , Buschmann H , Saint-Marcoux D , Ullrich KK , Haas FB , Vanderstraeten L , Becker D , Lang D , Vosolsobe S , Rombauts S , Wilhelmsson PKI , Janitza P , Kern R , Heyl A , Rumpler F , Villalobos L , Clay JM , Skokan R , Toyoda A , Suzuki Y , Kagoshima H , Schijlen E , Tajeshwar N , Catarino B , Hetherington AJ , Saltykova A , Bonnot C , Breuninger H , Symeonidi A , Radhakrishnan GV , Van Nieuwerburgh F , Deforce D , Chang C , Karol KG , Hedrich R , Ulvskov P , Glockner G , Delwiche CF , Petrasek J , Van de Peer Y , Friml J , Beilby M , Dolan L , Kohara Y , Sugano S , Fujiyama A , Delaux PM , Quint M , Theissen G , Hagemann M , Harholt J , Dunand C , Zachgo S , Langdale J , Maumus F , Van Der Straeten D , Gould SB , Rensing SA
Ref : Cell , 174 :448 , 2018
Abstract : Land plants evolved from charophytic algae, among which Charophyceae possess the most complex body plans. We present the genome of Chara braunii; comparison of the genome to those of land plants identified evolutionary novelties for plant terrestrialization and land plant heritage genes. C. braunii employs unique xylan synthases for cell wall biosynthesis, a phragmoplast (cell separation) mechanism similar to that of land plants, and many phytohormones. C. braunii plastids are controlled via land-plant-like retrograde signaling, and transcriptional regulation is more elaborate than in other algae. The morphological complexity of this organism may result from expanded gene families, with three cases of particular note: genes effecting tolerance to reactive oxygen species (ROS), LysM receptor-like kinases, and transcription factors (TFs). Transcriptomic analysis of sexual reproductive structures reveals intricate control by TFs, activity of the ROS gene network, and the ancestral use of plant-like storage and stress protection proteins in the zygote.
ESTHER : Nishiyama_2018_Cell_174_448
PubMedSearch : Nishiyama_2018_Cell_174_448
PubMedID: 30007417
Gene_locus related to this paper: chabu-a0a388kgf1 , chabu-a0a388jwy2

Title : Distinct contributions of A314S and novel R667Q substitutions of acetylcholinesterase 1 to carbofuran resistance of Chilo suppressalis Walker - Dai_2016_Pest.Manag.Sci_72_1421
Author(s) : Dai SM , Chang C , Huang XY
Ref : Pest Manag Sci , 72 :1421 , 2016
Abstract : BACKGROUND: In the striped stem borer, Chilo suppressalis, A314S, R667Q and H669P substitutions in acetylcholinesterase 1 (CsAChE1) have been associated with >1000-fold resistance against carbofuran. In this study, eight variants of CsAChE1 carrying different combinations of these substitutions were cloned and expressed using the Bac-to-Bac expression system to verify their contributions.
RESULTS: The expressed AChE1s had molecular weights of ca 160 kDa per dimer and 80 kDa per monomer. AChE kinetics and inhibition analysis showed that the A314S mutation was the key substitution responsible for a 15.1-fold decrease in hydrolytic activity to acetylthiocholine iodide and a 10.6-fold increase in carbofuran insensitivity of CsAChE. Compared with wild-type CsAChE1, this substituted CsAChE1 also showed 23.0-, 3.3- and 2.6-fold insensitivity to methomyl, triazophos and chlorpyrifos-oxon respectively. It should be noted that the R667Q substitution conferred a capability to increase the activity of wild-type and A314S-substituted CsAChE, while the A314S substitution reduced Km and compensated for overall catalytic efficiency. CONCLUSION: With the enhancing activity of the R667Q substitution, A314S is the major CsAChE1 substitution responsible for fitness-cost compensation and increased insensitivity to AChE inhibitors. The lower insensitivity of A314S-substituted CsAChE1 to chlorpyrifos-oxon suggests that chlorpyrifos could be an alternative insecticide for managing carbofuran-resistant field C. suppressalis in Taiwan. (c) 2015 Society of Chemical Industry.
ESTHER : Dai_2016_Pest.Manag.Sci_72_1421
PubMedSearch : Dai_2016_Pest.Manag.Sci_72_1421
PubMedID: 26446949

Title : Brain networks. Correlated gene expression supports synchronous activity in brain networks - Richiardi_2015_Science_348_1241
Author(s) : Richiardi J , Altmann A , Milazzo AC , Chang C , Chakravarty MM , Banaschewski T , Barker GJ , Bokde AL , Bromberg U , Buchel C , Conrod P , Fauth-Buhler M , Flor H , Frouin V , Gallinat J , Garavan H , Gowland P , Heinz A , Lemaitre H , Mann KF , Martinot JL , Nees F , Paus T , Pausova Z , Rietschel M , Robbins TW , Smolka MN , Spanagel R , Strohle A , Schumann G , Hawrylycz M , Poline JB , Greicius MD
Ref : Science , 348 :1241 , 2015
Abstract : During rest, brain activity is synchronized between different regions widely distributed throughout the brain, forming functional networks. However, the molecular mechanisms supporting functional connectivity remain undefined. We show that functional brain networks defined with resting-state functional magnetic resonance imaging can be recapitulated by using measures of correlated gene expression in a post mortem brain tissue data set. The set of 136 genes we identify is significantly enriched for ion channels. Polymorphisms in this set of genes significantly affect resting-state functional connectivity in a large sample of healthy adolescents. Expression levels of these genes are also significantly associated with axonal connectivity in the mouse. The results provide convergent, multimodal evidence that resting-state functional networks correlate with the orchestrated activity of dozens of genes linked to ion channel activity and synaptic function.
ESTHER : Richiardi_2015_Science_348_1241
PubMedSearch : Richiardi_2015_Science_348_1241
PubMedID: 26068849

Title : Amino acid substitutions and intron polymorphism of acetylcholinesterase1 associated with mevinphos resistance in diamondback moth, Plutella xylostella (L.) - Yeh_2014_Pestic.Biochem.Physiol_112_7
Author(s) : Yeh SC , Lin CL , Chang C , Feng HT , Dai SM
Ref : Pestic Biochem Physiol , 112 :7 , 2014
Abstract : The diamondback moth, Plutella xylostella L., is the most destructive insect pest of Brassica crops in the world. It has developed resistance rapidly to almost every insecticide used for its control. Mevinphos, a fast degrading and slow resistance evocating organophosphorus insecticide, has been recommended for controlling P. xylostella in Taiwan for more than 40years. SHM strain of P. xylostella, with ca. 22-fold resistance to this chemical, has been established from a field SH strain by selecting with mevinphos since 1997. Three mutations, i.e., G892T, G971C, and T1156T/G leading to A298S, G324A, and F386F/V amino acid substitutions in acetylcholinesterase1 (AChE1), were identified in these two strains; along with three haplotype pairs and a polymorphic intron in AChE1 gene (ace1). Two genetically pure lines, i.e., an SHggt wild type with intron AS and an SHMTCN mutant carrying G892T, G971C, T1156T/G mutations and intron AR in ace1, were established by single pair mating and haplotype determination. The F1 of SHMTCN strain had 52-fold resistance to mevinphos in comparison with the F1 of SHggt strain. In addition, AChE1 of this SHMTCN population, which exhibited lower maximum velocity (Vmax) and affinity (Km), was less susceptible to the inhibition of mevinphos, with an I50 32-fold higher than that of the SHggt F1 population. These results imply that amino acid substitutions in AChE1 of SHMTCN strain are associated with mevinphos resistance in this insect pest, and this finding is important for insecticide resistance management of P. xylostella in the field.
ESTHER : Yeh_2014_Pestic.Biochem.Physiol_112_7
PubMedSearch : Yeh_2014_Pestic.Biochem.Physiol_112_7
PubMedID: 24974111

Title : Amino acid substitutions of acetylcholinesterase associated with carbofuran resistance in Chilo suppressalis - Chang_2014_Pest.Manag.Sci_70_1930
Author(s) : Chang C , Cheng X , Huang XY , Dai SM
Ref : Pest Manag Sci , 70 :1930 , 2014
Abstract : BACKGROUND: Over 1000-fold carbofuran resistance has been observed in Chilo suppressalis (Walker) collected from the Changhua (CH) and Chiayi (CY) prefectures of Taiwan. An understanding of the pertinent mechanisms will benefit effective insecticide resistance management of C. suppressalis.
RESULTS: Among the five amino acid substitutions of acetylcholinesterase (AChE) identified in C. suppressalis, A314S and H668P had been reported and E101D, F402V and R667Q were novel. Substitution frequencies in AChE of CH and CY populations were much higher than in the susceptible Hsinchu (HC) population. Significantly negative correlations were observed between the frequencies of E101D, A314S and R667Q and the kinetic parameters of AChEs in these populations. AChE from the resistant CH population was less susceptible to the inhibition of carbofuran, with an I50 that was 3.6-fold higher than that of the susceptible HC population. Although Km and Vmax of AChE from the CH and CY populations were reduced to 72-87% of those from the HC population, the overall catalytic efficiency (Vmax /Km ) remained constant for all three populations. CONCLUSION: Amino acid substitutions identified in the AChE of C. suppressalis are associated with changes in AChE kinetics and its insensitivity to carbofuran. These observations are helpful for rapid monitoring, prediction and management of OP and CB resistance in the field. (c) 2014 Society of Chemical Industry.
ESTHER : Chang_2014_Pest.Manag.Sci_70_1930
PubMedSearch : Chang_2014_Pest.Manag.Sci_70_1930
PubMedID: 24616070

Title : Continuous production of lipase-catalyzed biodiesel in a packed-bed reactor: optimization and enzyme reuse study - Chen_2011_J.Biomed.Biotechnol_2011_
Author(s) : Chen HC , Ju HY , Wu TT , Liu YC , Lee CC , Chang C , Chung YL , Shieh CJ
Ref : J Biomed Biotechnol , 2011 : , 2011
Abstract : An optimal continuous production of biodiesel by methanolysis of soybean oil in a packed-bed reactor was developed using immobilized lipase (Novozym 435) as a catalyst in a tert-butanol solvent system. Response surface methodology (RSM) and Box-Behnken design were employed to evaluate the effects of reaction temperature, flow rate, and substrate molar ratio on the molar conversion of biodiesel. The results showed that flow rate and temperature have significant effects on the percentage of molar conversion. On the basis of ridge max analysis, the optimum conditions were as follows: flow rate 0.1 mL/min, temperature 52.1 degrees C, and substrate molar ratio 1 : 4. The predicted and experimental values of molar conversion were 83.31 +/- 2.07% and 82.81 +/- .98%, respectively. Furthermore, the continuous process over 30 days showed no appreciable decrease in the molar conversion. The paper demonstrates the applicability of using immobilized lipase and a packed-bed reactor for continuous biodiesel synthesis.
ESTHER : Chen_2011_J.Biomed.Biotechnol_2011_
PubMedSearch : Chen_2011_J.Biomed.Biotechnol_2011_
PubMedID: 20936129

Title : Functional and structural characterization of four glutaminases from Escherichia coli and Bacillus subtilis - Brown_2008_Biochemistry_47_5724
Author(s) : Brown G , Singer A , Proudfoot M , Skarina T , Kim Y , Chang C , Dementieva I , Kuznetsova E , Gonzalez CF , Joachimiak A , Savchenko A , Yakunin AF
Ref : Biochemistry , 47 :5724 , 2008
Abstract : Glutaminases belong to the large superfamily of serine-dependent beta-lactamases and penicillin-binding proteins, and they catalyze the hydrolytic deamidation of L-glutamine to L-glutamate. In this work, we purified and biochemically characterized four predicted glutaminases from Escherichia coli (YbaS and YneH) and Bacillus subtilis (YlaM and YbgJ). The proteins demonstrated strict specificity to L-glutamine and did not hydrolyze D-glutamine or L-asparagine. In each organism, one glutaminase showed higher affinity to glutamine ( E. coli YbaS and B. subtilis YlaM; K m 7.3 and 7.6 mM, respectively) than the second glutaminase ( E. coli YneH and B. subtilis YbgJ; K m 27.6 and 30.6 mM, respectively). The crystal structures of the E. coli YbaS and the B. subtilis YbgJ revealed the presence of a classical beta-lactamase-like fold and conservation of several key catalytic residues of beta-lactamases (Ser74, Lys77, Asn126, Lys268, and Ser269 in YbgJ). Alanine replacement mutagenesis demonstrated that most of the conserved residues located in the putative glutaminase catalytic site are essential for activity. The crystal structure of the YbgJ complex with the glutaminase inhibitor 6-diazo-5-oxo- l-norleucine revealed the presence of a covalent bond between the inhibitor and the hydroxyl oxygen of Ser74, providing evidence that Ser74 is the primary catalytic nucleophile and that the glutaminase reaction proceeds through formation of an enzyme-glutamyl intermediate. Growth experiments with the E. coli glutaminase deletion strains revealed that YneH is involved in the assimilation of l-glutamine as a sole source of carbon and nitrogen and suggested that both glutaminases (YbaS and YneH) also contribute to acid resistance in E. coli.
ESTHER : Brown_2008_Biochemistry_47_5724
PubMedSearch : Brown_2008_Biochemistry_47_5724
PubMedID: 18459799

Title : Saturated fat-rich diet enhances selective uptake of LDL cholesteryl esters in the arterial wall - Seo_2005_J.Clin.Invest_115_2214
Author(s) : Seo T , Qi K , Chang C , Liu Y , Worgall TS , Ramakrishnan R , Deckelbaum RJ
Ref : J Clinical Investigation , 115 :2214 , 2005
Abstract : Plasma LDL levels and atherosclerosis both increase on a saturated fat-rich (SAT) diet. LDL cholesterol delivery to tissue may occur via uptake of the LDL particles or via selective uptake (SU), wherein cholesteryl ester (CE) enters cells without concomitant whole-particle uptake. It is not known how dietary fats might directly affect arterial LDL-CE uptake and whether SU is involved. Thus, mice that are relatively atherosclerosis resistant (C57BL/6) or susceptible to atherosclerosis (apoE) were fed a chow or SAT diet and injected with double radiolabeled or fluorescent-labeled human LDL to independently trace LDL-CE core and whole-particle uptake, respectively. Our results show that a SAT diet increased contributions of SU to total arterial LDL-CE delivery in C57BL/6 and apoE mice. The SAT diet increased plasma fatty acid and cholesterol levels; cholesterol, but not fatty acid, levels correlated with SU, as did the degree of atherosclerosis. Increased SU did not correlate with arterial scavenger receptor class B type I levels but paralleled increased lipoprotein lipase (LPL) levels and LPL distribution in the arterial wall. These studies suggest that arterial LDL-CE delivery via SU can be an important mechanism in vivo and that dietary influences on arterial LPL levels and atherogenesis modulate arterial LDL-CE delivery, cholesterol deposition, and SU.
ESTHER : Seo_2005_J.Clin.Invest_115_2214
PubMedSearch : Seo_2005_J.Clin.Invest_115_2214
PubMedID: 16041409

Title : In vivo and in vitro properties of an intravenous lipid emulsion containing only medium chain and fish oil triglycerides - Ton_2005_Clin.Nutr_24_492
Author(s) : Ton MN , Chang C , Carpentier YA , Deckelbaum RJ
Ref : Clin Nutr , 24 :492 , 2005
Abstract : BACKGROUND & AIMS: The triglyceride (TG) fatty acyl composition in lipid emulsions influences their metabolism. Little is known about the effects of long chain omega-3 polyunsaturated fatty acids (PUFA) on lipid emulsion metabolism. We investigated possible differences between omega-3 containing emulsions in their metabolism and tissue-targeting in vivo in a mouse model, and in vitro using lipolysis and cell culture experiments.
METHODS: Soy oil (LCT), MCT/LCT/omega-3 (5:4:1, wt/wt/wt), and MCT/omega-3 (8:2, wt/wt) emulsions were radiolabeled with nondegradable 1alpha,2alpha (n)-[3H] cholesteryl oleoyl ether to trace core particle metabolism in C57BL/6J mice following a bolus injection. Blood samples obtained over 25 min and extracted organs were used to measure the tissue distribution of lipid emulsion particles. Lipoprotein lipase (LpL)-mediated hydrolysis experiments and cell uptake studies in cultured J774 murine macrophages were also performed.
RESULTS: Blood clearance of 8:2 was 13.4% and 29.8% faster compared to 5:4:1 and LCT, respectively. LCT had greatest liver uptake. LpL-mediated hydrolysis was greatest in 8:2 and lowest in LCT. Overall, cell TG accumulation in the presence of apolipoprotein E was least with 8:2.
CONCLUSIONS: Our data shows that 8:2 had the most efficient blood clearance but less hepatic uptake in vivo. In vitro, 8:2 had both highest hydrolysis by LpL and intracellular TG utilization in the presence of apoE. Thus, an 8:2 lipid emulsion undergoes efficient blood clearance and may direct omega-3 PUFA more towards extrahepatic tissues.
ESTHER : Ton_2005_Clin.Nutr_24_492
PubMedSearch : Ton_2005_Clin.Nutr_24_492
PubMedID: 16054521

Title : Altered N-myc downstream-regulated gene 1 protein expression in African-American compared with caucasian prostate cancer patients - Caruso_2004_Clin.Cancer.Res_10_222
Author(s) : Caruso RP , Levinson B , Melamed J , Wieczorek R , Taneja S , Polsky D , Chang C , Zeleniuch-Jacquotte A , Salnikow K , Yee H , Costa M , Osman I
Ref : Clin Cancer Research , 10 :222 , 2004
Abstract : PURPOSE: The protein encoded by N-myc downstream-regulated gene 1 (NDRG1) is a recently discovered protein whose transcription is induced by androgens and hypoxia. We hypothesized that NDRG1 expression patterns might reveal a biological basis for the disparity of clinical outcome of prostate cancer patients with different ethnic backgrounds. EXPERIMENTAL DESIGN: Patients who underwent radical prostatectomy between 1990 and 2000 at Veterans Administration Medical Center of New York were examined. We studied 223 cases, including 157 African Americans and 66 Caucasians (T2, n = 144; >/=T3, n = 79; Gleason <7, n = 122; >/=7, n = 101). Three patterns of NDRG1 expression were identified in prostate cancer: (a) intense, predominately membranous staining similar to benign prostatic epithelium; (b) intense, nucleocytoplasmic localization; and (c) low or undetectable expression. We then examined the correlations between patients' clinicopathological parameters and different NDRG1 expression patterns.
RESULTS: In this study of patients with equal access to care, African-American ethnic origin was an independent predictor of prostate-specific antigen recurrence (P < 0.05). We also observed a significant correlation between different patterns of NDRG1 expression and ethnic origin. Pattern 2 was less frequent in African Americans (21% versus 38%), whereas the reverse was observed for pattern 3 (60% in African Americans versus 44% in Caucasians; P = 0.03). This association remained significant after controlling for both grade and stage simultaneously (P = 0.02).
CONCLUSIONS: Our data suggest that different NDRG1 expression patterns reflect differences in the response of prostatic epithelium to hypoxia and androgens in African-American compared with Caucasian patients. Further studies are needed to determine the contribution of NDRG1 to the disparity in clinical outcome observed between the two groups.
ESTHER : Caruso_2004_Clin.Cancer.Res_10_222
PubMedSearch : Caruso_2004_Clin.Cancer.Res_10_222
PubMedID: 14734473

Title : De novo synthesis of ubiquitin carboxyl-terminal hydrolase isozyme l1 in rostral ventrolateral medulla is crucial to survival during mevinphos intoxication - Chang_2004_Shock_22_575
Author(s) : Chang C , Chang AY , Chan SH
Ref : Shock , 22 :575 , 2004
Abstract : Ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCH-L1) is a deubiquitinating enzyme that is responsible for making ubiquitin, which is required to target proteins for degradation by the ubiquitin-proteasome pathway in neurons, available. We investigated whether UCH-L1 plays a neuroprotective role at the rostral ventrolateral medulla (RVLM), the origin of sympathetic neurogenic vasomotor tone in the medulla oblongata where the organophosphate insecticide mevinphos (Mev) acts to elicit cardiovascular toxicity. In Sprague-Dawley rats maintained under propofol anesthesia, Mev (960 microg/kg, i.v.) induced a parallel and progressive augmentation in UCH-L1 or ubiquitin expression at the ventrolateral medulla during the course of Mev intoxication. The increase in UCH-L1 level was significantly blunted on pretreatment with bilateral microinjection into the RVLM of a transcription inhibitor, actinomycin D (5 nmol), or a translation inhibitor, cycloheximide (20 nmol). Compared with aCSF or sense oligonucleotide (100 pmol) pretreatment, microinjection of an antisense uch-L1 oligonucleotide (100 pmol) bilaterally into the RVLM significantly increased mortality, reduced the duration of the "pro-life" phase, blunted the increase in ubiquitin expression in ventrolateral medulla, and augmented the induced hypotension in rats that received Mev. These findings suggest that de novo synthesis of UCH-L1, leading to an enhanced disassembly of ubiquitin-protein conjugates in the RVLM, is essential to maintenance of the "pro-life" phase of Mev intoxication via prevention of cardiovascular depression, leading to neuroprotection.
ESTHER : Chang_2004_Shock_22_575
PubMedSearch : Chang_2004_Shock_22_575
PubMedID: 15545831

Title : Cloning and characterization of TDD5, an androgen target gene that is differentially repressed by testosterone and dihydrotestosterone - Lin_1997_Proc.Natl.Acad.Sci.U.S.A_94_4988
Author(s) : Lin TM , Chang C
Ref : Proc Natl Acad Sci U S A , 94 :4988 , 1997
Abstract : By using mRNA polymerase chain reaction differential display technique (DDPCR), we have identified one early responsive cDNA fragment, TDD5, from a 5alpha-reductase-deficient T cell hybridoma. The DDPCR profiles of TDD5 suggest that its expression can be repressed by testosterone (T) within 2 hr. More importantly, both DDPCR and Northern blot analysis further demonstrated that the expression of TDD5 was differentially repressed by T and dihydrotestosterone (DHT) at the mRNA level. To our knowledge, this is the first androgen target gene to show a preference in response to T over DHT in cell culture. TDD5 is expressed in several tissues with particular abundance in kidney. Full-length TDD5 cDNA (2,916 bp) encodes a protein with a calculated molecular weight of 42,000. Finally, our animal studies further confirm that TDD5 mRNA levels can be repressed to the basal level 8 hr after DHT administration. The isolation and characterization of the early-responsive androgen target gene TDD5 and the fact that TDD5 mRNA level can be differentially regulated by T and DHT may provide a useful tool to study the molecular mechanism of androgen preference on target gene regulation.
ESTHER : Lin_1997_Proc.Natl.Acad.Sci.U.S.A_94_4988
PubMedSearch : Lin_1997_Proc.Natl.Acad.Sci.U.S.A_94_4988
PubMedID: 9144177
Gene_locus related to this paper: mouse-ndr1