Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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Mammalian glycosyltransferases have been implicated in a wide variety of functions besides N-linked glycosylation, including developmental processes. For this reason, we studied the effects of cell cycle and entry into the cell cycle on beta 1-4-galactosyltransferase gene expression. In this study we report that beta 1-4-galactosyltransferase (GalTase) gene expression is, indeed, regulated during the normal cell cycle, peaking during late G1-, S, and early G2 phase of the cell cycle. In addition, GalTase gene expression is regulated in a manner that resembles other "early response" genes such as jun and fos upon reentry into the cell cycle from quiescence. Finally, we show that the GalTase gene is differentially expressed during murine embryogenesis and in terminally differentiated adult tissues. It is most abundant in testis, followed by skeletal muscle and spleen. The reasons for this pattern of differential expression in adult tissues are unknown. These studies should provide important new information regarding GalTase gene expression, its regulation, and its potential link to other developmental functions.
Somat Cell Mol Genet 1991 Sep
PMID:Beta 1-4-galactosyltransferase gene expression is regulated during entry into the cell cycle and during the cell cycle. 176 84

Transforming growth factor-beta (TGF beta) is a member of a large family of growth factors, several of which regulate pituitary function. TGF beta has recently been reported to reduce PRL production by GH4 cells. We have examined the effect of TGF beta on PRL gene expression in rat pituitary tumor GH3 cells. TGF beta 1 or TGF beta 2 reduced both basal and Ca(2+)-stimulated PRL mRNA levels. This inhibition was specific, as the mRNA levels for GH, glucose-regulated protein 78, and histone-3 were unaffected by TGF beta. Inhibition of PRL gene expression by TGF beta was dose dependent in the range of 0.5-10 ng/ml. TGF beta inhibited run-on PRL gene transcription in nuclei from treated cells to the same extent that it reduced PRL mRNA levels, indicating a transcriptional mechanism of action. However, TGF beta did not affect Pit-1 mRNA levels or run-on transcription of the Pit-1 gene. Thus, TGF beta does not appear to act through modification of Pit-1 gene expression. The PRL promotor contains two regions of homology, with a consensus sequence found in the promoters of other TGF beta-inhibited genes. These findings are consistent with other studies that have demonstrated transcriptional repression by TGF beta. The potency and specificity of the effects of TGF beta on PRL gene expression suggest that it may be a physiological regulator of lactotroph function.
Mol Endocrinol 1991 Nov
PMID:Inhibition of prolactin gene transcription by transforming growth factor-beta in GH3 cells. 177 73

We have studied the expression of transforming growth factor (TGF)-beta 1, -beta 2, and -beta 3 in the non-lactating and lactating bovine mammary gland by in situ hybridization. All three isoforms were expressed in the lobuloalveolar framework of the non-lactating and lactating gland although marked differences were apparent in their spatial distribution. TGF-beta 1 was expressed predominantly by the epithelial cells of the lobules although expression was also observed in the intralobular stroma cells lining the epithelium. In contrast, TGF-beta 2 expression was only observed in the epithelial cells. TGF-beta 3 transcripts were expressed at the highest levels and were observed in almost all cells of the lobule. No TGF-beta signals were found in the interlobular regions of the mammary gland. The possible regulatory functions of these molecules in development of the mammary gland and on differentiation processes in the neonate are discussed.
Mol Cell Endocrinol 1991 Dec
PMID:Localization of transforming growth factor-beta 1, -beta 2 and -beta 3 gene expression in bovine mammary gland. 179 9

A decrease in the density of the beta 1-adrenergic receptor and an increase in the functional activity of the G inhibitory protein Gi accompany human heart failure; however, the molecular and biochemical mechanisms responsible for these changes are unclear. We previously reported that the steady-state levels of the mRNAs encoding both alpha Gi-3 and alpha Gs were significantly increased in failing human heart. However, these results are not consistent with recent studies demonstrating that immunodetectable levels of alpha G proteins are not different in failing human hearts when compared with non-failing controls. In addition, analysis of the 5' flanking regions of alpha Gi and alpha Gs suggests that these two genes are unlikely to be co-regulated as their regulatory domains are quite different. Therefore, we hypothesized that the disparity between the measurements of alpha G protein gene expression and assessment of the actual levels of alpha G proteins might be due to technical limitations of the Northern blot technique utilized in previous studies for assessment of the mRNA levels; (i) cytoskeletal beta-actin mRNA was used as a standard for normalization; and (ii) only relative levels of alpha G mRNAs were measured. The recent application of the polymerase chain reaction to quantification of mRNA levels in small quantities of human heart provided the tool with which to test this hypothesis. When expressed in molecules of mRNA per microgram of total RNA, there were no differences in the levels of alpha Gi and alpha Gs mRNAs in failing human heart when compared with non-failing controls.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Cardiol 1991 Dec
PMID:Expression of alpha-subunits of G proteins in failing human heart: a reappraisal utilizing quantitative polymerase chain reaction. 181 Oct 54

Using the thyroid follicular cell as a model for multi-stage carcinogenesis, we have investigated the role of two potential negative growth regulators ('anti-oncogenes') in epithelial tumour progression--transforming growth factor-beta 1 (TGF beta 1) and p53. Normal follicular cells, as expected, showed marked growth inhibition in response to TGF beta 1. Adenoma cells were equally inhibited. In contrast, spontaneously and SV40-immortalised follicular cell lines showing features of malignant transformation (notably loss of growth factor dependence) had lost all responsiveness to TGF beta 1, accompanied by a partial loss of its receptors. p53 protein was below detectable limits in normal and in adenoma cells but in contrast very high levels were observed in all three transformed lines. In the SV40-immortalised cells, this was expected in view of the known stabilising effect of the viral large T protein. In the spontaneous line we found strong evidence for point mutation of p53, which is known to have the same effect. Both mechanisms result in loss of p53 tumour suppressor function despite increased protein content. We conclude that loss of inhibition by TGF beta and inactivation of p53 are important steps in in vitro immortalisation and/or in vivo tumour progression in human thyroid follicular cells, and speculate that p53 may mediate or be required for the inhibitory signal normally induced by TGF beta 1.
Mol Cell Endocrinol 1991 Apr
PMID:Correlated abnormalities of transforming growth factor-beta 1 response and p53 expression in thyroid epithelial cell transformation. 182 Sep 69

Two specific beta-N-acetylglucosaminyltransferases involved in the branching and elongation of mucin oligosaccharide chains, namely, a beta 1,6 N-acetylglucosaminylsaminyltransferase that transfers N-acetylglucosamine from UDP-N-acetylglucosamine to Gal beta 3GalNAc-mucin to yield Gal beta 3(GlcNAc beta 6)GalNAc-Mucin and a beta 3-N-acetylglucosaminyl transferase that transfers N-acetylglucosamine from UDP-N-acetylglucosamine to Gal beta 3(GlcNAc beta 6)GalNAc-mucin to yield GlcNAc beta 3Gal beta 3 (GlcNAc beta 6)GalNAc-Mucin were purified from the microsomal fraction of swine trachea epithelium. The beta 1,6-N-acetylglucosaminyltransferase was purified about 21,800-fold by procedures which included affinity chromatography on DEAE columns containing bound asialo Cowper's gland mucin glycoprotein with Gal beta 1,3GalNAc side chains. The apparent molecular weight estimated by gel filtration was found to be about 60 Kd. The purified enzyme showed a high specificity for Gal beta 1,3GalNAc chains and the most active substrates were mucin glycoproteins containing these chains. The apparent Km of the beta 6-glucosaminyltrans-ferase for Cowper's gland mucin glycoprotein containing Gal beta 1,3GalNAc chains was 0.53 microM; for UDP-N-acetylglucosamine, 12 microM; and for Gal beta 1,3GalNAc alpha NO2 phi, 4 mM. The activity of the beta 6-glucosaminyltransferase was dependent on the extent of glycosylation of the Gal beta 3GalNAc chains in Cowper's gland mucin glycoprotein. The best substrate for the partially purified beta 3-Glucosaminyltransferase was Cowper's gland mucin glycoprotein containing Gal beta 1,3(GlcNAc beta 6)GalNAc side chains. This enzyme showed little or no activity with intact sialylated Cowper's gland mucin glycoprotein or derivatives of this glycoprotein containing GalNAc or Gal beta 1,3GalNAc side chains. The radioactive oligosaccharides formed by these enzymes in large scale reaction mixtures were released from the mucin glycoproteins by treatment with alkaline borohydride, isolated by gel filtration on Bio-Gel P-6 and characterized by methylation analysis and sequential digestion with exoglycosidases. The oligosaccharide products formed by the beta 6- and beta 3-glucosaminyltransferases were shown to be Gal beta 3(GlcNAc beta 6) GalNAc and GlcNAc beta 3 Gal beta 3(GlcNAc beta 6)GalNAc respectively. Taken collectively, these results demonstrate that swine trachea epithelium contains two specific N-acetylglucosaminyltransferases which catalyze the initial branching and elongation reactions involved in the synthesis of O-linked oligosaccharide chains in respiratory mucin glycoproteins. The first enzyme a beta 6-glucosaminyltransferase converts Gal beta 3GalNAc chains in mucin glycoproteins to Gal beta 3(GlcNAc beta 6)GalNAc chains.(ABSTRACT TRUNCATED AT 400 WORDS)
Mol Cell Biochem 1991 Mar 13
PMID:UDP-GlcNAc: Gal beta 3GalNAc-mucin: (GlcNAc----GalNAc) beta 6-N-acetylglucosaminyltransferase and UDP-GlcNAc: Gal beta 3(GlcNAc beta 6) GalNAc-mucin (GlcNAc----Gal)beta 3-N-acetylglucosaminyltransferase from swine trachea epithelium. 183 Jun 37

Expression of the E1A gene of adenovirus type 5 (Ad5) in a cloned rat embryo fibroblast (CREF) cell line results in morphological transformation. The efficiency of E1A-mediated transformation of CREF cells is increased if a wild-type Ad5 E1A gene is cotransfected with a rat beta 1 protein kinase C (beta 1 PKC) gene. A direct demonstration of complementation between a functional-transforming Ad5 E1A gene and beta 1 PK in inducing transformation was demonstrated using Ad5 E1A cold-sensitive mutant (E1Acs) genes. The E1Acs gene enhanced transformation only at the transformation-permissive temperature of 37 degrees C and not at the nonpermissive transforming temperature of 32 degrees C. CREF cells constitutively expressing low levels of beta 1 PKC mRNA were transformed at a higher frequency than parental CREF cells after transfection with an Ad5 E1A gene or infection with wild-type Ad5 or the Ad5 host-range cold-sensitive mutant H5hr1. There was no enhancement of transformation in low-level beta 1 PKC-expressing CREF cells when cultures were grown continuously in the presence of the PKC-inhibitor 1-(5-isoquinolynsulfonyl)-2-methylpiperazine dihydrochloride. Transfected CREF cells expressing low levels of beta 1 PKC mRNA displayed CREF-like morphology and did not form colonies when grown in agar. In contrast, retroviral vector-transformed CREF cells expressing high levels of beta 1 PKC mRNA and beta 1 PKC enzyme activity were morphologically transformed and grew efficiently in agar. These findings indicate that the beta 1 PKC gene, when expressed at low levels, can cooperate with the Ad5 E1A gene in the initiation of viral oncogene-mediated transformation.
Mol Carcinog 1991
PMID:Low-level beta 1 protein kinase C expression in cloned rat embryo fibroblast cells enhances transformation induced by the adenovirus type 5 E1A gene. 183 66

Transforming growth factor-beta (TGF beta) is a potent growth inhibitor in most epithelial cells. We evaluated the effects of norethindrone (which in combination with estrogen is commonly used in oral contraceptives) and other progestins [medioxyprogesterone acetate (MPA) and R5020, which are not used in oral contraceptives] on cell growth and the expression of TGF beta 1, TGF beta 2, and TGF beta 3 mRNAs in MCF-7 human breast cancer cells. Growth of MCF-7 cells was stimulated by norethindrone (10(-8)-10(-5) M), with maximal growth stimulation at 10(-7) M norethindrone after 7 days of treatment. However, the growth of MCF-7 cells was not affected by MPA (10(-8) M) or R5020 (10(-8) M). Treatment with the antiestrogen 4-hydroxytamoxifen at a concentration of 10(-7) M blocked the growth stimulation induced by norethindrone. The norethindrone-induced growth stimulation was accompanied by a dramatic decrease in TGF beta 2 and TGF beta 3 mRNA levels, whereas the level of TGF beta 1 mRNA was not affected by any of the compounds tested. In addition, treatment with MPA or R5020 did not affect TGF beta 2 and TGF beta 3 mRNA levels. The inhibitory effect of norethindrone on TGF beta 2 and TGF beta 3 mRNA levels could be blocked by the addition of 10(-7) M 4-hydroxytamoxifen. Norethindrone as well as estradiol decreased estrogen receptor mRNA levels and increased progesterone receptor mRNA levels. This is the first report which demonstrates that norethindrone stimulates estrogen-responsive human breast cancer cell growth and inhibits the expression of TGF beta 2 and TGF beta 3 mRNAs. These results suggest that the differential regulation of TGF beta expression by norethindrone may be at least partly responsible for the growth stimulation induced by norethindrone. Thus, the norethindrone component of some oral contraceptives may be sufficiently estrogenic to facilitate the development of breast cancer.
Mol Endocrinol 1991 Aug
PMID:Growth stimulation and differential regulation of transforming growth factor-beta 1 (TGF beta 1), TGF beta 2, and TGF beta 3 messenger RNA levels by norethindrone in MCF-7 human breast cancer cells. 183 33

The beta-tubulin genes G beta 1 and G beta 2 from the phytopathogenic hemiascomycete Geotrichum candidum were found to be highly diverged in amino acid sequence from those of other filamentous fungi. G beta 1 and G beta 2 were also divergent from each other, with the coding regions sharing only 66% nucleotide sequence homology and 64% amino acid identity. However, the proteins shared 82% similarity and only 25 of the 161 non-identical amino acid substitutions were non-conservative. The organization of G beta 1 is similar to other fungal beta-tubulin genes, but G beta 2 has several unusual features; it has 2 amino acid additions in the N-terminal 40 residues and must employ an uncommon 5' splice junction sequence in preference to an overlapping perfect consensus. The amino acid change found to confer benomyl resistance in Neurospora crassa was also present in G beta 2. G beta 1 has four introns which are located similarly to those of beta-tubulin genes in other fungi. G beta 2, however, has a single intron in a unique location. Translational fusions employing the 5' non-coding regions of the two Geotrichum beta-tubulin genes were made with the hygromycin phosphotransferase gene and shown to function in Schizosaccharomyces pombe and Trichoderma hamatum. However, G. candidum could not be transformed with these or other tested plasmids commonly used for fungal transformation.
Mol Gen Genet 1991 Nov
PMID:Characterization of two beta-tubulin genes from Geotrichum candidum. 183 49

Gap junctions are widely distributed structures that mediate communication between cells. The channels that allow passage of small molecules between adjacent cells are made up of oligomeric proteins (connexins) that are encoded by a family of related genes. By probing somatic cell hybrid DNA on Southern filters with rat or human cDNAs or human genomic fragments, we have mapped four functioning gap junction genes, (alpha 1, beta 1, beta 2, and alpha 3), to different sites on human chromosomes: GJA1 (connexin43) to 6p21.1-q24.1; GJB1 (connexin32) to Xcen-q22; GJB2 (connexin26) to 13; and GJA3 (connexin46) also to 13, probably near GJB2. The GJA3 probe also hybridized to a restriction fragment that was mapped to chromosome 1. A GJA1-related pseudogene GJA1P was assigned to chromosome 5. The homologous loci in mouse were assigned to regions of known conserved syntenic groups: Gja-1 to chromosome 10; Gjb-1 to XD-F4 and Gjb-2 to 14. Of two sites of hybridization with the GJA3 probe, on mouse 14 and 5, we assume that the site on 14 corresponds to the GJA3 locus on human 13. Based on these data, additional members of this family of related genes can be isolated and characterized, and possible human and mouse mutations can be identified.
Somat Cell Mol Genet 1991 Mar
PMID:Distribution of genes for gap junction membrane channel proteins on human and mouse chromosomes. 184 21


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