Abstract：
:A common cause for pharmacogenetic alteration in drug response is genetic variation in encoded amino acid sequence. We have used the catecholamine and drug-metabolizing enzyme sulfotransferase (SULT)1A3 to create an artificial model system to study mechanisms-especially possible aggresome formation-by which genetic alteration in amino acid sequence might influence function. Specifically, we created a double variant SULT1A3 allozyme that included the naturally occurring Asn234 polymorphism plus an additional Trp172Arg mutation. Analysis of the SULT1A3 X-ray crystal structure had indicated that the Trp172Arg mutation might destabilize the protein's structure. Expression of SULT1A3 Arg172,Asn234 in COS-1 cells resulted in undetectable enzyme activity and a virtual lack of enzyme protein. Rabbit reticulocyte lysate degradation studies showed that the double variant allozyme was degraded much more rapidly than was wild type SULT1A3 by a ubiquitin-proteasome-dependent process. In addition, after expression in COS-1 cells, the double variant allozyme localized to aggresomes, a process not previously described or studied in pharmacogenetics. Therefore, the alteration of only one or two amino acids can lead to decreased levels of protein as a result of both aggresome formation and accelerated degradation. The possible role of aggresome formation in pharmacogenetics should be evaluated in naturally occurring systems with inherited alteration in encoded amino acid sequence.
journal_name
Biochem Biophys Res Communjournal_title
Biochemical and biophysical research communicationsauthors
Wang L,Yee VC,Weinshilboum RMdoi
10.1016/j.bbrc.2004.10.040subject
Has Abstractpub_date
2004-12-10 00:00:00pages
426-33issue
2eissn
0006-291Xissn
1090-2104pii
S0006-291X(04)02321-6journal_volume
325pub_type
杂志文章abstract：:A small fraction of tumor cells are thought to possess the potential for both multiple-lineage differentiation and self-renewal, which underlies the cancer stem cell hypothesis. However, the differentiation mechanisms of these cells have not been elucidated due to a lack of appropriate culture methods. Here, we establ...
journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1016/j.bbrc.2016.11.106
更新日期：2017-01-22 00:00:00
abstract：:Septins, a conserved family of GTPases, are heteropolymeric filament-forming proteins that associate with the cell membrane and cytoskeleton and serve essential functions in cell division and morphogenesis. Their roles in fungal cell wall chitin deposition, septation, cytokinesis, and sporulation have been well establ...
journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1016/j.bbrc.2011.01.017
更新日期：2011-02-11 00:00:00
abstract：:Bordetella pertussis, causative agent of whooping cough, produces an adenylate cyclase toxin (CyaA) that is an important virulence factor. In the host cell, the adenylate cyclase domain of CyaA (CyaA-ACD) is activated upon association with calmodulin (CaM), an EF-hand protein comprised of N- and C-lobes (N-CaM and C-C...
journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1016/j.bbrc.2014.09.048
更新日期：2014-10-10 00:00:00
abstract：:Soluble guanylyl cyclase (sGC) is activated by nitric oxide (NO) and generates the second messenger cyclic GMP (cGMP). Recently, purified sGC α1β1 has been shown to additionally generate the cyclic pyrimidine nucleotides cCMP and cUMP. However, since cyclic pyrimidine nucleotide formation occurred only the presence of...
journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1016/j.bbrc.2013.12.108
更新日期：2014-01-24 00:00:00
abstract：:We previously reported that Ca2+/calmodulin-dependent protein kinase II (CaMKII) is inhibited by S-nitrosylation of Cys6 in cells. Herein, we show that polysulfidation of CaMKII at Cys6 limits its enzyme activity following reactive sulfur species (RSS) stimulus. In vitro incubation of CaMKII with the RSS donor, Na2S4,...
journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1016/j.bbrc.2018.11.134
更新日期：2019-01-08 00:00:00
abstract：:Green tea catechins have been shown to attenuate obesity in animals and humans. The catechins activate adenosine monophosphate-activated protein kinase (AMPK), and thereby increase fatty acid oxidation in liver and skeletal muscles. Green tea catechins have also been shown to reduce body fat in humans. However, the ef...
journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1016/j.bbrc.2015.03.158
更新日期：2015-05-22 00:00:00
abstract：:Leucine-rich repeat kinase 2 (LRRK2) is the molecule responsible for autosomal-dominant Parkinson's disease (PD), PARK8, but the etiologic effects of its mutation remain unknown. In the present study, we investigated a novel mechanism for the neurodegeneration induced by I2020T mutant LRRK2. Using native gel electroph...
journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1016/j.bbrc.2012.11.113
更新日期：2013-01-11 00:00:00
abstract：:We have established that differing effects of alpha1-adrenergic receptor (AR) subtypes on cell proliferation are due to differential coupling to the Gs/cAMP pathway; thus, both alpha1A- and alpha1B-ARs couple to Gs, while alpha1D-AR does not. To identify the region responsible for this difference in subtype-specific G...
journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1016/s0006-291x(02)02589-5
更新日期：2002-11-22 00:00:00
abstract：:We examined the intracellular localization of the myosin binding subunit (MBS) of smooth muscle myosin phosphatase. In MDCK cells in a confluent monolayer of polarized epithelial sheet, MBS was concentrated to the cell-cell adhesion sites. Double-immunofluorescence analysis with anti-MBS and anti-beta-catenin antibodi...
journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1006/bbrc.1996.5986
更新日期：1997-01-23 00:00:00
abstract：:The effect of immune interferon (IFN-gamma) and recombinant tumor necrosis factor (rTNF-alpha) on cellular differentiation was investigated in human promyelocytic leukemia cell line HL-60. Both IFN-gamma and rTNF-alpha induced the appearance of the monocytic phenotype in a dose- and time-dependent manner as assessed b...
journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1016/0006-291x(86)90721-7
更新日期：1986-11-14 00:00:00
abstract：:The IGF-I receptor binds IGF-I with complex kinetics characterized by a curvilinear Scatchard plot, suggesting receptor heterogeneity and apparent negative cooperativity. To explore the molecular mechanisms underlying these properties, we have characterized the binding of a hybrid receptor formed from a wild-type rece...
journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1016/j.bbrc.2005.03.122
更新日期：2005-05-27 00:00:00
abstract：:We found that both RNA and cDNA preparations derived from melanocytes contain a RT-PCR inhibitor that copurified with nucleic acids. Investigation of the candidate inhibitor melanin revealed that it potently blocks PCR at concentrations below 200 ng/ml, whereas 100 microg/ml melanin was required to inhibit reverse tra...
journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1006/bbrc.2000.2716
更新日期：2000-05-19 00:00:00
abstract：:To obtain antiparallel and parallel dimers of alpha-human atrial natriuretic peptide (alpha-hANP), two fully protected peptides I and II having the same amino acid sequence as alpha-hANP with different protective groups at the cysteinyl residues were synthesized, the former having Acm and Npys and the latter MeBzl and...
journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1016/s0006-291x(86)80224-8
更新日期：1986-12-15 00:00:00
abstract：:The secreted isoform of fibroblast growth factor 3 (FGF3) induces a mitogenic cell response, while the nuclear form inhibits cell proliferation. Recently, we identified a nucleolar FGF3-binding protein which is implicated in processing of pre-rRNA as a possible target of nuclear FGF3 signalling. Here, we report a seco...
journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1016/j.bbrc.2005.10.079
更新日期：2005-12-16 00:00:00
abstract：:Human PTK7 is a defective receptor protein tyrosine kinase and its expression is upregulated in various cancers including colorectal carcinomas. To determine whether PTK7 functions in angiogenesis, we have expressed and purified the extracellular domain of PTK7 (soluble PTK7; sPTK7) as a decoy receptor to counteract t...
journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1016/j.bbrc.2008.04.168
更新日期：2008-07-11 00:00:00
abstract：:Ras can become activated via multiple distinct receptors in T lymphocytes. However, mechanistic studies of Ras signaling in normal T cells have been hampered by the lack of an efficient technology for gene transfer into resting post-thymic cells. We have overcome this limitation by utilizing adenoviral transduction of...
journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1016/j.bbrc.2003.10.168
更新日期：2003-12-19 00:00:00
abstract：:Dexamethasone (DEX) induces apoptosis in lymphocytes, while protecting some cancer cells from apoptosis, by a poorly understood mechanism. In this study, we examined the potential role of the forkhead transcription factor (FOXO3A) in DEX-induced apoptosis. Unphosphorylated FOXO3A, the active form of FOXO3A, can transl...
journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1016/j.bbrc.2008.10.097
更新日期：2008-12-19 00:00:00
abstract：:Inactivation of serotonin transporter (HTT) by pharmacologically in the neonate or genetically increases risk for depression in adulthood, whereas pharmacological inhibition of HTT ameliorates symptoms in depressed patients. The differing role of HTT function during early development and in adult brain plasticity in c...
journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1016/j.bbrc.2008.01.041
更新日期：2008-03-28 00:00:00
abstract：:Helical hairpins, two closely spaced helical membrane spanning segments separated by a short surface turn, are thought to be common in integral membrane proteins. Here, we study the membrane integration of a naturally occurring helical hairpin from the secretory Na(+)-K(+)-2Cl(-) cotransporter NKCC1. This sequence is ...
journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1016/j.bbrc.2007.02.149
更新日期：2007-05-04 00:00:00
abstract：:An organic extract of Nitzschia alba cells possesses ionophoretic activity towards silicate, as it induces silicate transport across an organic phase or across synthetic lipid membranes. The activity is dependent upon Na+ and prefers silicon to germanium, a congener. The activity can be resolved into two apparently pu...
journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1016/0006-291x(83)91636-4
更新日期：1983-07-18 00:00:00
abstract：:In the brain angiotensin converting enzyme is highly localized to a striatonigral pathway, which contains no endogenous angiotensin. Substance P, also localized to a striatonigral pathway, is degraded by ACE via two different pathways. The lung and striatal isozymes of angiotensin converting enzyme exhibit differentia...
journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1016/0006-291x(85)91681-x
更新日期：1985-04-16 00:00:00
abstract：:VEGF family members play important roles in angiogenesis and vascular permeability. VEGF-A-transgenic mice showed an increased vascularization with edema due to hyper-vascular permeability and subcutaneous hemorrhage as side effects. VEGF-A binds and activates two receptors, VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1). To...
journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1016/s0006-291x(02)03033-4
更新日期：2003-02-07 00:00:00
abstract：:Sugars will eventually be exported transporters (SWEETs) are a group of recently identified sugar transporters in plants that play important roles in diverse physiological processes. However, currently, limited information about this gene family is available in pineapple (Ananas comosus). The availability of the recen...
journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1016/j.bbrc.2018.01.024
更新日期：2018-02-05 00:00:00
abstract：:Aminoglycoside phosphotransferases represent a broad class of enzymes that promote bacterial resistance to aminoglycoside antibiotics via the phosphorylation of hydroxyl groups in the latter. Here we report the spatial structure of the 3'-aminoglycoside phosphotransferase of novel VIII class (AphVIII) solved by X-ray ...
journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1016/j.bbrc.2016.06.097
更新日期：2016-09-02 00:00:00
abstract：:Activins, TGF-beta superfamily members, have multiple functions in a variety of cells and tissues. Recently, additional activin beta subunit genes, betaC and betaE, have been identified. To explore the role of activin E, we created transgenic mice overexpressing human activin betaE subunit. There were pronounced diffe...
journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1016/j.bbrc.2005.12.205
更新日期：2006-03-10 00:00:00
abstract：:Centrin is an EF-hand calcium-binding protein found in microtubule organizing centers of organisms ranging from algae and yeast to man. Phosphorylation in the centrin C-terminal domain occurs in mitosis and is associated with alterations in contractile fibers. To obtain insight into the structural basis for the functi...
journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1016/j.bbrc.2006.01.155
更新日期：2006-03-31 00:00:00
abstract：:A bioassay based on the measurement of thymidine incorporation into trichloroacetic acid-insoluble materials in erythroid cell suspensions from fetal calf liver was used as the assay for purification of two small peptides (erythrotropins I and II) from fetal calf intestine. The peptides were purified using reversed-ph...
journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1016/s0006-291x(83)80169-7
更新日期：1983-09-15 00:00:00
abstract：:The calcium-sensing receptor (CaR) is a G protein-coupled receptor that plays key roles in extracellular calcium ion (Ca(2+)(o)) homeostasis by enabling parathyroid, kidney, and other cells to directly "sense" changes in Ca(2+)(o). In multiple myeloma-associated bone disease, myeloma cells could raise the level of Ca(...
journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1016/s0006-291x(02)02690-6
更新日期：2002-12-13 00:00:00
abstract：:Replacement of leucine in the chemotactic peptide For-Met-Leu-Phe by the sterically constrained amino acids alpha-aminoisobutyric acid and aminocyclohexanecarboxylic acid affords compounds of equal or greater activity than the parent. NMR studies indicate that the parent compound is present as a beta-sheet in solution...
journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1016/s0006-291x(88)80287-0
更新日期：1988-12-15 00:00:00
abstract：:A spontaneous lymphoma was detected in mice, which was caused by a recessive autosomal mutation. The genetic basis was revealed to be a 5-bp deletion at the splicing donor site of the first intron of the FasL gene, resulting in aberrant transcripts coding for non-functional proteins. This mutation of the FasL gene cau...
journal_title：Biochemical and biophysical research communications
pub_type： 杂志文章
doi：10.1016/j.bbrc.2006.07.215
更新日期：2006-10-13 00:00:00
