Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Murine erythroleukemia cells were induced to undergo erythroid differentiation by growing in presence of dimethylsulfoxide, butyric acid or actinomycin D. topological linking numbers in closed loops of nuclear DNA were measured by means of centrifugation of nucleoids containing superhelical DNA in sucrose gradients containing varying concentrations of ethidium bromide. All cells were grown to G1 stage of the cell cycle. It was found that the mean density of the DNA topological linking number decreases from 0.076 turns per 10 nucleotide pairs in non-differentiated cells to 0.062 turns in the cells induced to differentiate. This decrease in topological linking number of DNA loops is quite sufficient for the change in the DNA double helix secondary structure which in turn may be responsible for coordinate switch in transcription of genes which control cellular differentiation (Luchnik, 1980a, b).
Mol Gen Genet 1980
PMID:Decrease in the number of DNA topological turns during Friend erythroleukemia differentiation. 693 May 35

Factors involved in the selection of the 20 protein L-alpha-amino acids during chemical evolution and the early stages of Darwinian evolution are discussed. The selection is considered on the basis of the availability in the primitive ocean, function in proteins, the stability of the amino acid and its peptides, stability to racemization, and stability on the transfer RNA. We conclude that aspartic acid, glutamic acid, arginine, lysine, serine and possibly threonine are the best choices for acidic, basic and hydroxy amino acids. The hydrophobic amino acids are reasonable choices, except for the puzzling absences of alpha-amino-n-butyric acid, norvaline and norleucine. The choices of the sulfur and aromatic amino acids seem reasonable, but are not compelling. Asparagine and glutamine are apparently not primitive. If life were to arise on another planet, we would expect that the catalysts would be poly-alpha-amino acids and that about 75% of the amino acids would be the same as on the earth.
J Mol Evol 1981
PMID:Reasons for the occurrence of the twenty coded protein amino acids. 727 10

Recent cloning of the cDNAs for the two isozymes of steroid 5 alpha-reductase (EC 1.3.99.5) allowed individual expression of the isozymes and permitted us to investigate the action of steroid 5 alpha-reductase inhibitors against the individual isozymes without any ambiguity that may be caused by coexistence of the isozymes in tissue preparations. We examined the kinetic characteristics of FK143 (4-[3-[3-[bis(4-isobutylphenyl)methylamino]benzoyl]-1H-indol-1- yl]butyric acid), a novel nonsteroidal steroid 5 alpha-reductase inhibitor against cloned human and rat steroid 5 alpha-reductase isozymes. FK143 was shown to inhibit both isozymes equally. The mode of the inhibition of FK143 against both isozymes was noncompetitive. The inhibition constants Kie and Kies of FK143 for human types 1 and 2 were 27.0 and 19.6 nM and 19.9 and 14.5 nM, respectively. Species selectivity between human and rat of the inhibitory activity of FK143 against both isozymes was not found. We also examined the effect of FK143 on the in vivo expression of the genes encoding for the rat steroid 5 alpha-reductase isozymes. FK143 reduced the testosterone-induced increase in the amount of the type 1 mRNA in castrated rat, whereas it did not substantially affect the amount of the type 2 mRNA.
Mol Pharmacol 1995 Sep
PMID:Novel steroid 5 alpha-reductase inhibitor FK143: its dual inhibition against the two isozymes and its effect on transcription of the isozyme genes. 756 19

Two-dimensional 1H NMR spectra of an analog of reduced BPTI at pH 4.5, 1 degrees C, have been assigned. Spectra indicate considerable conformational averaging, as expected for a flexible, unfolded protein. The presence of extensive nonrandom structure is detected by the presence of NHi-NHi + 1 and aromatic-aliphatic NOEs. Sequential amide-amide NOEs indicate that turn-like conformations are significantly populated at 18 pairs of residues along the chain. Many of these are located in a turn, loop, or helix in native BPTI, but six are observed for contiguous pairs in the segment composed of residues 29-35, which in native BPTI constitute a strand of extended sheet. A novel finding for unfolded proteins is our observation of NOEs implying non-native hydrophobic interactions. Multiple aromatic-aliphatic NOEs are observed for pairs of residues that are within 1-3 residues of each other. Most are non-native and involve residues in both strands of the central antiparallel strand-turn-strand of native BPTI comprised of residues 18-35. All NOEs reported for oligopeptides spanning the BPTI sequence [Kemmink, J., & Creighton, T. (1993) J. Mol. Biol. 234, 861-878] are observed in reduced BPTI, but many others are present as well. Similar spectra are obtained for naturally occurring BPTI reduced by dithiothreitol, BPTI with cysteines replaced by alpha-amino-n-butyric acid, and BPTI mutant F45A reduced by dithiothreitol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Extensive nonrandom structure in reduced and unfolded bovine pancreatic trypsin inhibitor. 757 94

The PRB-1b gene codes for a basic-type pathogenesis-related protein of the PR-1 family of tobacco. PRB-1b mRNA accumulation is induced in response to biotic and abiotic elicitors, such as TMV, ethylene, salicylic acid, alpha-amino butyric acid and darkness. In order to determine the location of elements that control dark-regulated PRB-1b gene expression, we tested promoter, transcribed regions and 3'-downstream regions of the gene for their ability to respond to dark induction in transgenic tobacco plants. An ethylene-inducible promoter region of 863 bp was not able to confer dark induction to a beta-glucuronidase reporter gene, while a construct containing the transcribed region of the gene and 3'-downstream sequences, driven by the cauliflower mosaic virus 35S promoter, was correctly dark-regulated. The results indicate that dark-induction of the PRB-1b gene can be controlled by 3'-downstream elements at the transcriptional level or by transcribed sequences at the post-transcriptional level. A circadian clock regulation of the PRB-1b gene was excluded, as fluctuations of PRB-1b transcript levels were not observed in plants placed in constant light or darkness. Subcellular localization of the PRB-1b protein was also determined, in tobacco protoplasts preparations and in cell cultures. The PRB-1b polypeptide was predominantly detected in protoplast vacuoles and was not secreted to the media in cell cultures. These results support an intracellular localization for the PRB-1b protein, as reported for other basic-type components of the pathogenesis-related proteins family.
Plant Mol Biol 1995 Jun
PMID:Dark induction and subcellular localization of the pathogenesis-related PRB-1b protein. 763 22

Straight-chain, non-natural, nonpolar amino acids norleucine, norvaline, and alpha-amino-n-butyric acid at various spacings do not interact with themselves to stabilize helix formation in alanine-based peptides, but do interact with a Tyr spaced i, i + 4 to stabilize alanine helices, similar to the helix-stabilizing i, i + 4 Tyr-Leu and Tyr-Val interactions reported earlier (Padmanabhan S, Baldwin RL, 1994, J Mol Biol 241:706-713). Leu spaced i, i + 4 from another Leu is measurably helix-stabilizing relative to the corresponding i, i + 3 pair, but less so than for i, i + 4 Val-Leu, Ile-Leu, or Phe-Leu pairs (relative to the corresponding i, i + 3 pairs) when Leu is C-terminal to the other nonpolar amino acid. Our results indicate that limited side-chain flexibility in an alpha-helix strongly favors the interaction between 2 nonpolar residues to stabilize an isolated alpha-helix.
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PMID:Tests for helix-stabilizing interactions between various nonpolar side chains in alanine-based peptides. 770 46

The cytotoxic efficacy of antitumor drugs targeted at DNA topoisomerase II (topo II) in many cases varies in direct proportion to cellular topo II content. To investigate the transcriptional control of the predominant alpha form of topo II, the 5' flanking region of the human topo II alpha gene (positions -562 to +90) was subcloned into a firefly luciferase reporter plasmid and transiently transfected into HL-60 human leukemia cells, a line capable of monocytic differentiation after treatment with various agents. Early in phorbol-12-myristate-13-acetate (30 nM)-induced differentiation (18-24 hr after treatment), an unexpected 3-5-fold activation of topo II alpha gene promoter activity was observed. Activation was observed in HL-60 cells and U-937 cells, but not in HeLa human cervical carcinoma cells. Sodium butyrate (NaB) (0.4 mM) also led to activation (4-17-fold) of the topo II alpha promoter in HL-60 and U-937 cells. Promoter sequences between position -90 and position +90 mediated the inducing effects of NaB. This NaB-dependent promoter-reporter induction was partly mirrored by a transient approximately 2-fold increase in endogenous topo II alpha enzyme. The stimulus for promoter activation could be partly attributed to a 2-fold increase in DNA synthesis at 16 hr for NaB, but not phorbol-12-myristate-13-acetate. Regardless of the primary stimulus for topo II alpha promoter trans-activation, it could be bypassed by treatment of HL-60 cells with NaB for 48 hr before transfection, revealing the expected 60-70% suppression of topo II alpha promoter activity. Further study of topo II alpha promoter down-regulation later in monocytic differentiation may serve as a model for elucidating the transcriptional mechanisms that may also be exploited by tumor cells expressing intrinsic or acquired resistance to topo II-directed drugs.
Mol Pharmacol 1995 Apr
PMID:Topoisomerase II alpha promoter trans-activation early in monocytic differentiation of HL-60 human leukemia cells. 772 30

We have used a tumorigenic glioblastoma cell line, SNB-19, as a model system to identify fucose-containing glycoprotein candidates for tumor suppressor function. Glycoproteins were analyzed after treatment with a variety of chemical differentiating agents by two-dimensional SDS-PAGE, followed by electroblotting and visualization using the fucose-specific lectin, Ulex europeaus I. Approximately 25 fucose-containing glycoproteins (FUCGLAPs) were routinely visualized in control extracts using 60-70 micrograms of protein per gel and staining with Vectastain ABC kits. Retinoic acid induced the most marked change in FUCGLAP expression, causing a fivefold increase in one FUCGLAP (M(r) = 125 kDa, pI = 6.6). Neither butyric acid, dibutyryl cAMP, nor combinations of these compounds gave a similar result. Using this model system and analytical approach, it should be possible to identify, isolate, and evaluate glycoprotein oligosaccharides for their tumor modulating capability.
Mol Chem Neuropathol
PMID:The identification of glioblastoma-associated, fucose-containing glycoproteins induced by retinoic acid. 808 41

Sodium butyrate is known to induce morphological and biochemical changes associated with cell differentiation in some colon tumor cell lines including HT29. In our present study we observed that sodium butyrate treatment caused a decrease in the level of expression of RB1 gene on day seven of butyrate treatment but a gradual six to sevenfold decrease in the level of expression of p53 gene. Western blot analysis revealed a decrease in the level of the phosphorylated form of Rb protein (pRb) and an increase in the level of underphosphorylated pRb as compared to the control cells. These changes in the phosphorylation level were observed from day three of sodium butyrate treatment. In addition, the flat foci forming large differentiated cells also began to appear after 3 days of sodium butyrate treatment. In this study, we are able to show that, besides induction of differentiation, sodium butyrate treatment can also cause a reversal in the phosphorylation status of the pRb in colon tumor cell line HT29. These results suggest that the phosphorylation level of pRb could be associated with the cell differentiation process in human colonic epithelium and as a consequence in its neoplastic development.
Cell Mol Biol (Noisy-le-grand) 1993 Sep
PMID:Effect of sodium butyrate on the expression of retinoblastoma (RB1) and P53 gene and phosphorylation of retinoblastoma protein in human colon tumor cell line HT29. 822 69

During dimethyl sulfoxide (DMSO)-stimulated differentiation of murine erythroleukemia (MEL) cells, one of the early events is the induction of the heme biosynthetic pathway. While recent reports have clearly demonstrated that GATA-1 is involved in the induction of erythroid cell-specific forms of 5-aminolevulinate synthase (ALAS-2) and porphobilinogen (PBG) deaminase and that cellular iron status plays a regulatory role for ALAS-2, little is known about regulation of the remainder of the pathway. In the current study, we have made use of a stable MEL cell mutant (MEAN-1) in which ALAS-2 enzyme activity is not induced by DMSO, hexamethylene bisacetamide (HMBA), or butyric acid. In this cell line, addition of 2% DMSO to growing cultures results in the normal induction of PBG deaminase and coproporphyrinogen oxidase but not in the induction of the terminal two enzymes, protoporphyrinogen oxidase and ferrochelatase. These DMSO-treated cells did not produce mRNA for beta-globin and do not terminally differentiate. In addition, the cellular level of ALAS activity declines rapidly after addition of DMSO, indicating that ALAS-1 must turn over rapidly at this time. Addition of 75 microM hemin alone to the cultures did not induce cells to terminally differentiate or induce any of the pathway enzymes. However, the simultaneous addition of 2% DMSO and 75 microM hemin caused the cells to carry out a normal program of terminal erythroid differentiation, including the induction of ferrochelatase and beta-globin. These data suggest that induction of the entire heme biosynthetic pathway is biphasic in nature and that induction of the terminal enzymes may be mediated by the end product of the pathway, heme. We have introduced mouse ALAS-2 cDNA into the ALAS-2 mutant cell line (MEAN-1) under the control of the mouse metallothionein promoter (MEAN-RA). When Cd and Zn are added to cultures of MEAN-RA in the absence of DMSO, ALAS-2 is induced but erythroid differentiation does not occur and cells continue to grow normally. In the presence of metallothionein inducers and DMSO, the MEAN-RA cells induce in a fashion similar to that found with the wild-type 270 MEL cells. Induction of the activities of ALAS, PBG deaminase, coproporphyrinogen oxidase, and ferrochelatase occurs. In cultures of MEAN-RA where ALAS-2 had been induced with Cd plus Zn 24 h prior to DMSO addition, onset of heme synthesis occurs more rapidly than when DMSO and Cd plus Zn are added simultaneously. This study reveals that induction of ALAS-2 alone is not sufficient to induce terminal differentiation of the MEAN-RA cells, and it does not appear that ALAS-2 alone is the rate-limiting enzyme of the heme biosynthetic pathway during MEL cell differentiation.
Mol Cell Biol 1993 Nov
PMID:Biphasic ordered induction of heme synthesis in differentiating murine erythroleukemia cells: role of erythroid 5-aminolevulinate synthase. 841 1


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