Biomedical subjects

L B Chen

Publications and source records attributed to L B Chen.

At least 37 records · Page 2Linked to original sources

PubMed1999

Synthesis and evaluation of chalcogenopyrylium dyes as potential sensitizers for the photodynamic therapy of cancer.

A series of thiopyrylium (2), selenopyrylium (3), and telluropyrylium dyes (4) was prepared via the addition of Grignard reagents to either 2, 6-di(4-dimethylamino)phenylchalcogenopyran-4-ones (5a) or 2-[4-(dimethylamino)phenyl]-6-phenylchalcogenopyran-4-ones (5b) followed by elimination and ion exchange to give the chloride salts. The absorption spectra and quantum yields for singlet oxygen generation of these dyes suggested that the dyes would have utility as sensitizers for PDT. Selenopyrylium dyes 3a and 3d with quantum yields for singlet oxygen generation of 0.040 and 0.045, respectively, were phototoxic to Colo-26 cells in culture. The toxicity of the dyes 2-4 was evaluated in clonogenic assays of human carcinoma cell lines. Importantly, the presence of a sulfur, selenium, or tellurium heteroatom in the molecules had no predictable impact on the toxicity of any particular dye set. Substituents at the 2-, 4-, and 6-positions of the dye had a much greater impact on cytotoxicity. The IC(50) values determined in the clonogenic assays did not correlate with chemical properties in the dye molecules such as reduction potential or lipophilicity. Initial in vivo toxicity studies showed no toxicity for these dyes at dosages between 7.2 and 38 micromol/kg in BALB/c mice.

Aniline Compounds↗

PubMed1999

HRad17, a human homologue of the Schizosaccharomyces pombe checkpoint gene rad17, is overexpressed in colon carcinoma.

Using the palindromic PCR-cDNA display method, we have cloned a novel gene overexpressed by human colon carcinoma relative to normal colon. Among normal tissues examined, only testis expresses it at a high level. Sequence analysis revealed its extensive homology with checkpoint genes rad17 of Schizosaccharomyces pombe and RAD24 of Saccharomyces cerevisiae. This novel gene designated as hRad17 is localized to chromosome 5q12,13.1, a region known to be deleted in a variety of human cancers. Promoter region and one pseudogene of hRad17 have been identified. Whereas the increased expression of hRad17 by human colon carcinomas may be related to the known resistance of these cells to DNA-damaging agents during therapy, the deletion of hRad17 in a variety of cancers may predispose them to increased rate of mutation and heightened sensitivity to DNA-damaging agents, including radiation and anticancer drugs.

Animals↗

PubMed1999

Expression of the focal adhesion protein paxillin in lung cancer and its relation to cell motility.

Lung cancer can lead to abnormalities of the actin cytoskeleton structure which may be important in transformation. In this study, we have investigated the expression of the cytoskeletal associated protein paxillin in lung cancer. Paxillin is a 68 kDa focal adhesion protein, with four tandem LIM domains at the C-terminus, involved in growth factor receptor, integrin and oncogenic signaling such as v-src, BCR/ABL, and E6 of the papilloma virus. In non-small cell lung cancer (NSCLC) cell lines, paxillin localized to the focal adhesions. The possible role of paxillin in lung cancer cells was assessed by overexpressing green fluorescence protein (GFP)-paxillin construct in two separate NSCLC cell lines (Calu-1 and H661). Over the course of 48 h, GFP-paxillin consistently caused the cells to become round and to decrease cell motility as compared to normal controls, GFP-N-terminus paxillin, or GFP-LIM transfected cells. Because some lung cancers may be quite aggressive and metastasize quickly, which may be related to the cytoskeleton, we determined the expression of paxillin in NSCLC and small cell lung cancer (SCLC) cell lines and patient tumor tissues. Expression of paxillin in NSCLC and SCLC cell lines were determined by Northern blot and Western blot analysis. The expression of paxillin was consistently low in SCLC cell lines, whereas there was paxillin expression in NSCLC cell lines. There was a variability of expression of paxillin in NSCLC tumor tissue as compared to normal lung tissue. In contrast, by immunohistochemistry, we show that there was no detectable expression of paxillin in 5/5 SCLC patients. This data suggests that absence or low level of paxillin protein expression may cause certain lung cancers, such as SCLC, to be more motile and possibly more aggressive.

3T3 Cells↗

PubMed1999

Pharmacokinetic analysis and antitumor efficacy of MKT-077, a novel antitumor agent.

MKT-077 (1-ethyl-2-[[3-ethyl-5-(3-methylbenzothiazolin-2-yliden)]-4- oxothiazolidin-2-ylidenemethyl] pyridinium chloride), a novel rhodacyanine dye in phase I/II clinical trials, may provide a new approach to cancer therapy based on the accumulation in the mitochondria of the cells of certain carcinomas, for example, those of the colon, breast and pancreas. To support the development of MKT-077 for clinical application as an intravenous (i.v.) therapy, we investigated the metabolic fate of [14C]MKT-077 in BDF1 mice as well as the distribution of MKT-077 in experimental LS174T tumor-bearing mice using a high-performance liquid chromatography (HPLC) method. The plasma levels of 14C after i.v. administration of [14C]MKT-077 declined in a triphasic manner. In the first distribution phase, the levels of 14C decreased with a T1/2 of approximately 5 min. In the second and terminal phase, the T1/2 of 14C was 2.8-4.6 h and 16.2 h, respectively. Cmax (1 min after injection) increased from 0.3 to 1.5 microg/ml linearly, but less than proportionately between the doses. The AUC(0-infinity) at 0.3, 1 and 3 mg/kg were 0.030 +/- 0.002, 0.60 +/- 0.12 and 1.73 +/- 0.25 microg x h/ml, respectively. Plasma clearance was approximately 1.8 l/h per kg (at doses of 1 and 3 mg/kg). The steady state volume of distribution (6.8 and 25.1 l/kg) indicated that MKT-077 distributed as a lipid-soluble molecule. The mean residence time (MRT) was 4.1 (at a dose of 1 mg/kg) and 14.1 h (at a dose of 3 mg/kg). In the first rapid phase (5 min after dosing), 14C radioactivity was detected in most of the tissues and organs, most strongly in the kidney cortex, and not in the central nervous system and testes. In the terminal phase (24 h after dosing), 14C contents increased in the intestinal tract, and in the kidney and liver were nearly to the background level. After i.v. bolus administration at a dose of 3 mg/kg of [14C]MKT-077, the predominant route of elimination of the radioactivity was via the feces, and recoveries of total radioactivity in urine and feces corresponded to 33.5% and 61.1%, respectively. More than 60% was recovered within 24 h and 95% within 1 week. MKT-077 was primarily excreted in unmetabolized form with five unidentified metabolites found in the urine and plasma. Intact MKT-077 was retained in the tumor tissue longer than in plasma and kidney in LS174T tumor-bearing mice receiving MKT-077 at an i.v. therapeutic dose (10 mg/kg). This accumulation decreased very slowly, suggesting that the high membrane potentials of tumor cell mitochondria may help retain the drug in tumors.

Animals↗

PubMed1999

Determination of MKT-077, a novel antineoplastic agent, in plasma samples by high-performance liquid chromatography and its application to pharmacokinetics in rats.

A simple high-performance liquid chromatographic method was developed for determination of a novel antineoplastic agent MKT-077 in plasma. MKT-077 was extracted from 50 microl of plasma with acetonitrile containing 1 ml trifluoroacetic acid per liter. Chromatographic separation was achieved within 13.5 min using a reverse-phase Puresil C18 analytical column. A visible detector operated at 490 nm was used. The linearity of the calibration curve was obtained (r2 = 0.99986) over the analytical range of 10-500 ng/ml(-1). The intra- and inter-assay precision was in the range of 0.9-11.1 and 0.3-4.4%, respectively. The intra- and inter-assay bias ranged from -7.3 to 11.1% and from 0.4 to 11.6%, respectively. The utility of this assay was demonstrated after the administration of a single dose of MKT-077 to rats. The plasma elimination half-life of MKT-077 was 1.8-4 h.

Animals↗

PubMed1998

BAX expression is associated with enhanced intracellular accumulation of paclitaxel: a novel role for BAX during chemotherapy-induced cell death.

SW626 cells that overexpress BAX are sensitized to the cytotoxic effects of paclitaxel and vincristine. It has been assumed that BAX mediates these effects through its ability to alter mitochondrial function, specifically by promoting the release of cytochrome c and facilitating the mitochondrial permeability transition. However, we have found that several early paclitaxel-mediated events are enhanced in SW626 transfectants that overexpress BAX, including G2-M-phase arrest, tubulin polymerization, and BCL-2 phosphorylation. We now demonstrate that these seemingly disparate effects are explained by an enhanced accumulation of paclitaxel in BAX-overexpressing cells, an effect due to diminished drug efflux. In contrast, drug efflux is increased in cells that do not overexpress BAX, resulting in low intracellular paclitaxel levels and relative resistance to the effects of this drug. Drug efflux in SW626 cells is mediated by a verapamil-inhibitable, non-MDR-1, non-MRP-1 transporter whose function or expression may be inhibited by BAX. These data suggest that stable transfectants that overexpress BAX may be sensitized to apoptotic cell death through a novel mechanism involving the enhancement of intracellular levels of naturally occurring toxins such as alkaloid derivatives.

ATP-Binding Cassette Transporters↗

PubMed1998

The adenomatous polyposis coli-binding protein EB1 is associated with cytoplasmic and spindle microtubules.

The evolutionarily conserved protein EB1 originally was identified by its physical association with the carboxyl-terminal portion of the adenomatous polyposis coli (APC) tumor suppressor protein, an APC domain commonly mutated in familial and sporadic forms of colorectal neoplasia. The subcellular localization of EB1 in epithelial cells was studied by using immunofluorescence and biochemical techniques. EB1 colocalized both to cytoplasmic microtubules in interphase cells and to spindle microtubules during mitosis, with pronounced centrosome staining. The cytoskeletal array detected by anti-EB1 antibody was abolished by incubation of the cells with nocodazole, an agent that disrupts microtubules; upon drug removal, EB1 localized to the microtubule-organizing center. Immunofluorescence analysis of SW480, a colon cancer cell line that expresses only carboxyl-terminal-deleted APC unable to interact with EB1, demonstrated that EB1 remained localized to the microtubule cytoskeleton, suggesting that this pattern of subcellular distribution is not mediated by its interaction with APC. In vitro cosedimentation with taxol-stabilized microtubules demonstrated that a significant fraction of EB1 associated with microtubules. Recent studies of the yeast EB1 homologues Mal3 and Bim1p have demonstrated that both proteins localize to microtubules and are important in vivo for microtubule function. Our results demonstrate that EB1 is a novel component of the microtubule cytoskeleton in mammalian cells. Associating with the mitotic apparatus, EB1 may play a physiologic role connecting APC to cellular division, coordinating the control of normal growth and differentiation processes in the colonic epithelium.

Adenomatous Polyposis Coli↗

PubMed1998

The bis-azo compound FP-21399 inhibits HIV-1 replication by preventing viral entry.

The bis-azo compound FP-21399 inhibits HIV-1 infection. We now show that FP-21399 acts on the HIV-1 envelope glycoprotein to prevent viral replication. This compound targets the entry step of the HIV-1 replication cycle as demonstrated by time-of-addition and single cycle viral entry assays. The entry of SIVmac239, which uses the same coreceptors (CD4/CCR5) as HIV-1, was not inhibited by FP-21399, indicating that the antiviral effect of FP-21399 is specific for the HIV-1 envelope glycoprotein and is not dependent upon the cellular receptors CD4 and CCR5. FP-21399 inhibits neither the activity of HIV-1 reverse transcriptase nor the expression of HIV-1 early mRNA. Finally, this compound inhibits gp120 shedding of the T-tropic virus. Our results suggest that the anti-HIV activity of FP-21399 is due to its interaction with HIV-1 gp120/41 complex during viral entry.

Animals↗

PubMed1998

Structure-activity of novel rhodacyanine dyes as antitumor agents.

We have previously reported that rhodacyanine dyes, such as 1 and 2, exhibited a potent inhibitory effect on the growth of several tumor cells and that 4-oxothiazolidine (rhodanine) was an essential moiety for antitumor activity. On the basis of our foregoing work, two types of rhodacyanine dyes, which categorized into class I and II depending on the methine length, were synthesized and evaluated as a novel antitumor agent. Attention was particularly focused on the structure-activity study of two heteroaromatic rings. In class I, where the A rings were conjugated to rhodanine via two methine groups, compounds 1, 20, 23, and 24 were found to be efficacious in tumor-bearing nude mice model study, but they did not have the chemical properties (stability, solubility) suitable for clinical use. In contrast, in class II, where the A rings were directly conjugated to rhodanine, compounds 13 and 25, which possessed a benzothiazole moiety for the A ring, exhibited the favorable biological and chemical properties. Therefore, we decided to have a benzothiazole moiety as the A ring and introduce various heterocyclic groups for the B ring. As a result, the pyridinium ring was selected as the optimal moiety for the B ring (compound 13). Further, the variation of counteranion had a profound effect on solubility in water without influence on antitumor activity. Chloride anion was selected as the favorable anion with respect to synthetic method as well as solubility in water. Our study finally led us to the identification of compound 3 (MKT 077, 1-ethyl-2-[[3-ethyl-5-(methylbenzothiazolin-2-ylidene)-4-oxothi azolidin-2 -ylidene]methyl]pyridinium chloride) as the candidate for clinical trials and is currently subjected to further investigation as a potent antitumor agent in phase I clinical trial for the treatment of solid tumors.

Animals↗

PubMed1998

Photoactivation enhances the mitochondrial toxicity of the cationic rhodacyanine MKT-077.

In this study, the mitochondrial phototoxicity of the cationic rhodacyanine MKT-077 was investigated by comparing its effects on the inhibition of mitochondrial respiration and the structural integrity of mitochondrial DNA (mtDNA) in the presence and absence of added high-intensity visible light (7.5 J/cm2). Results indicate that photoirradiation significantly enhances the mitochondrial toxicity of MKT-077 at both the biochemical and DNA levels. For example, the concentration of MKT-077 required to achieve one-half maximal inhibition of ADP-stimulated respiration was observed to be 6-fold lower in the presence versus absence of high-intensity light (one-half maximal inhibition at 2.5 versus 15 microg MKT-077/ mg, respectively). In addition, photoirradiation produced a 25-fold increase in inhibition of succinate-cytochrome c reductase activity by MKT-077 (one-half maximal inhibition at 2 versus 50 microg MKT-077/ml, +/-light, respectively) and a 6-fold increase in inhibition of cytochrome oxidase activity (one-half maximal inhibition at 5 versus 30 microg MKT-077/ml, +/-light, respectively). Furthermore, the combination of 25 microg/ml MKT-077 and 7.5 J/cm2 visible light caused significant degradation of mtDNA in isolated rat liver mitochondria, whereas the same concentration of dye in the absence of light had only a modest effect on mtDNA. Evaluation of light-induced MKT-077 lipid peroxidation in mitochondrial membrane fragments by the thiobarbituric acid test and by measurement of nonrespiratory-linked oxygen uptake suggests that mitochondrial phototoxicity by MKT-077 may be the result of lipid peroxidation via reactive oxygen species. These results have important implications with regard to the potential use of MKT-077 in photochemotherapy.

Animals↗

PubMed1998

Differentiation and reversal of malignant changes in colon cancer through PPARgamma.

PPARgamma is a nuclear receptor that has a dominant regulatory role in differentiation of cells of the adipose lineage, and has recently been shown to be expressed in the colon. We show here that PPARgamma is expressed at high levels in both well- and poorly-differentiated adenocarcinomas, in normal colonic mucosa and in human colon cancer cell lines. Ligand activation of this receptor in colon cancer cells causes a considerable reduction in linear and clonogenic growth, increased expression of carcinoembryonic antigen and the reversal of many gene expression events specifically associated with colon cancer. Transplantable tumors derived from human colon cancer cells show a significant reduction of growth when mice are treated with troglitazone, a PPARgamma ligand. These results indicate that the growth and differentiation of colon cancer cells can be modulated through PPARgamma.

Adenocarcinoma↗

PubMed1998

S-1153 inhibits replication of known drug-resistant strains of human immunodeficiency virus type 1.

S-1153 is a new imidazole compound that inhibits human immunodeficiency virus (HIV) type 1 (HIV-1) replication by acting as a nonnucleoside reverse transcriptase inhibitor (NNRTI). This compound inhibits replication of HIV-1 strains that are resistant to nucleoside and nonnucleoside reverse transcriptase inhibitors. S-1153 has a 50% effective concentration in the range of 0.3 to 7 ng/ml for strains with single amino acid substitutions that cause NNRTI resistance, including the Y181C mutant, and also has potent activity against clinical isolates. The emergence of S-1153-resistant variants is slower than that for nevirapine, and S-1153-resistant variants contained at least two amino acid substitutions, including F227L or L234I. S-1153-resistant variants are still sensitive to the nucleoside reverse transcriptase inhibitors zidovudine (AZT) and lamivudine. In a mouse and MT-4 (human T-cell line) in vivo HIV replication model, S-1153 and AZT administered orally showed a marked synergy for the inhibition of HIV-1 replication. S-1153 shows a significant accumulation in lymph nodes, where most HIV-1 infection is thought to occur. S-1153 may be an appropriate candidate for two-to three-drug combination therapy for HIV infection.

Animals↗

PubMed1998

Inactivation of DNA-dependent protein kinase by protein kinase Cdelta: implications for apoptosis.

Protein kinase Cdelta (PKCdelta) is proteolytically cleaved and activated at the onset of apoptosis induced by DNA-damaging agents, tumor necrosis factor, and anti-Fas antibody. A role for PKCdelta in apoptosis is supported by the finding that overexpression of the catalytic fragment of PKCdelta (PKCdelta CF) in cells is associated with the appearance of certain characteristics of apoptosis. However, the functional relationship between PKCdelta cleavage and induction of apoptosis is unknown. The present studies demonstrate that PKCdelta associates constitutively with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs). The results show that PKCdelta CF phosphorylates DNA-PKcs in vitro. Interaction of DNA-PKcs with PKCdelta CF inhibits the function of DNA-PKcs to form complexes with DNA and to phosphorylate its downstream target, p53. The results also demonstrate that cells deficient in DNA-PK are resistant to apoptosis induced by overexpressing PKCdelta CF. These findings support the hypothesis that functional interactions between PKCdelta and DNA-PK contribute to DNA damage-induced apoptosis.

Apoptosis↗

PubMed1998

Clioquinol-zinc chelate: a candidate causative agent of subacute myelo-optic neuropathy.

BACKGROUND: 5-chloro-7-iodo-8-hydroxyquinoline (clioquinol) was used clinically three decades ago as an oral antiparasitic agent and to increase intestinal absorption of zinc in patients with acrodermatitis enteropathica, a genetic disorder of zinc absorption. Use of clioquinol was epidemiologically linked to subacute myelo-optic neuropathy (SMON), characterized by peripheral neuropathy and blindness, which affected 10,000 patients in Japan. Discontinuation of oral clioquinol use led to elimination of SMON, however, the mechanism of how clioquinol induces neurotoxicity is unclear. MATERIALS AND METHODS: We tested the effect of clioquinol-metal chelates on neural crest-derived melanoma cells. The effect of clioquinol chelates on cells was further studied by electron microscopy and by a mitochondrial potential-sensitive fluorescent dye. RESULTS: Of the ions tested, only clioquinol-zinc chelate demonstrated cytotoxicity. The cytotoxicity of clioquinol-zinc chelate was extremely rapid, suggesting that its primary effect was on the mitochondria. Electron microscopic analysis demonstrated that clioquinol-zinc chelate caused mitochondrial damage. This finding was further confirmed by the observation that clioquinol-zinc chelate caused a decrease in mitochondrial membrane potential. CONCLUSIONS: We demonstrate that clioquinol, in the presence of zinc, is converted to a potent mitochondrial toxin. The phenomenon of clioquinol mediated toxicity appears to be specific to zinc and is not seen with other metals tested. Since clioquinol has been shown to cause increased systemic absorption of zinc in humans, it is likely that clioquinol-zinc chelate was present in appreciable levels in patients with SMON and may be the ultimate causative toxin of SMON.

Chelating Agents↗

PubMed1997

Mouse hepatitis virus infection induces an early, transient calcium influx in mouse astrocytoma cells.

Mouse hepatitis virus (MHV), a murine coronavirus, utilizes murine carcinoembryonic antigens as receptors. The events that follow virus-receptor binding and eventually lead to virus entry are poorly understood. We studied the possible effects of MHV infection on intracellular calcium in a mouse astrocytoma cell line. Using the calcium-sensitive dye fluo-3 and confocal laser scanning microscopy, we found that MHV strain JHM induced an immediate (within 20 s) and transient (lasting no longer than 2 min) calcium increase in about 5% of the infected cells. The calcium increase was blocked by antibodies against the viral spike protein, suggesting that it was specifically triggered by the interaction of the viral spikes with cells. It was also inhibited by L-type calcium channel blockers and was not detected in calcium-free medium, suggesting that the calcium increase was caused by calcium influx from the extracellular medium. Studies of the kinetics of viral replication by immunofluorescence staining of the viral nucleocapsid protein revealed that at 3 h postinfection there was roughly the same percentage of cells (5%) that produced the viral protein as the percentage of cells that had responded with a calcium signal. This finding and the virus dilution studies together suggest that calcium responders may represent cells that had been infected with multiple viruses and undergone rapid viral replication. Furthermore, calcium channel blockers, including verapamil and cadmium chloride, and the calcium chelator EGTA inhibited virus infection. Therefore, the transient intracellular calcium increase reported here may be an early signaling event associated with virus infection.

Aniline Compounds↗

PubMed1997

Mutational evidence for control of cell adhesion through integrin diffusion/clustering, independent of ligand binding.

Previous studies have shown that integrin alpha chain tails make strong positive contributions to integrin-mediated cell adhesion. We now show here that integrin alpha4 tail deletion markedly impairs static cell adhesion by a mechanism that does not involve altered binding of soluble vascular cell adhesion molecule 1 ligand. Instead, truncation of the alpha4 cytoplasmic domain caused a severe deficiency in integrin accumulation into cell surface clusters, as induced by ligand and/ or antibodies. Furthermore, alpha4 tail deletion also significantly decreased the membrane diffusivity of alpha4beta1, as determined by a single particle tracking technique. Notably, low doses of cytochalasin D partially restored the deficiency in cell adhesion seen upon alpha4 tail deletion. Together, these results suggest that alpha4 tail deletion exposes the beta1 cytoplasmic domain, leading to cytoskeletal associations that apparently restrict integrin lateral diffusion and accumulation into clusters, thus causing reduced static cell adhesion. Our demonstration of integrin adhesive activity regulated through receptor diffusion/clustering (rather than through altered ligand binding affinity) may be highly relevant towards the understanding of inside-out signaling mechanisms for beta1 integrins.

Animals↗

PubMed1997

Synthesis and evaluation of novel rhodacyanine dyes that exhibit antitumor activity.

Rhodacyanine dyes and several analogous delocalized lipophilic cations (DLCs) were synthesized and evaluated as novel antitumor agents. Rhodacyanine dye consists of two heteroaromatic rings such as thiazoles at both termini of the conjugate systems and 4-oxothiazolidine (rhodanine) in the middle of it. Compounds with such a unique double-conjugate structure were found to inhibit the growth of several tumor cell lines, such as colon carcinoma CX-1, and to exhibit relatively low toxicity against normal kidney cell line CV-1 (e.g., IC50(CX-1) = 50 nM, IC50(CV-1) = 17.3 microM; selectivity index = 346 for compound 5). These compounds were also found to be efficacious in the tumor-bearing nude mice model (e.g., against human melanoma LOX; T/C (%) = 168 for compound 5). Structural modifications on rhodacyanine, including deletion of a heteroaromatic ring involved in the merocyanine conjugate system and replacement of rhodanine with a structurally related moiety such as 4-oxoimidazolidine or 4-oxo-1,3-dithiolane, resulted in a loss of the selectivity and/or the activity. Our current structure-activity studies imply that the double-conjugate system with a rhodanine moiety is essential for the selective activity of rhodacyanine dyes, and we find this class of compounds as unique antitumor agents candidates.

Animals↗

PubMed1997

Association of the mammalian helicase MAH with the pre-mRNA splicing complex.

Conversion of pre-mRNAs into mature mRNAs includes several consecutive enzymatic modification steps that are carried out in the spliceosomes. Helicases have been shown to contribute to these catalytic processes both in yeast and in mammalian cells. Our results identify the mammalian protein MAH (matrix-associated helicase) as a new helicase present in the spliceosome complex. Sequence comparison describes MAH as the first higher eukaryotic member of the helicase superfamily I, with demonstrated enzymatic activity. Because MAH does not bind small nuclear ribonucleoproteins (snRNPs), it appears to be a non-snRNP binding factor of the splicing complex. In conclusion, our data suggest the involvement of MAH in processing of pre-mRNAs in mammalian cells.

Animals↗