Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.17 (lysozyme)
 21,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The retroviral oncogene v-myb encodes a nuclear, sequence-specific DNA-binding protein. To investigate the possibility that v-myb encodes a transcriptional regulator, we used a transient cotransfection assay to explore the potential of v-myb to influence the expression of other genes. We found that expression of a chicken lysozyme promoter/CAT gene construct was activated by v-myb in the presence of myb-specific binding sites. Action was not observed with a truncated v-myb protein lacking its DNA-binding domain. We also observed that expression of a hybrid human HSP70 promoter/CAT gene, lacking myb-specific binding sites, was activated by v-myb. However, in this case, the truncated v-myb protein, which lacked its DNA-binding domain, also activated HSP70/CAT expression, indicating that trans-activation of this gene construct was independent of the sequence-specific DNA-binding activity of the v-myb protein. These observations suggest that v-myb encodes a trans-activator and that activation of gene expression occurs by two different mechanisms, one of which involves specific binding of v-myb protein to the regulated gene.
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PMID:Activation of transcription by v-myb: evidence for two different mechanisms. 248 27

Structural, dynamic and energetic properties of proteins in solution can be studied in atomic detail by molecular dynamics computer simulation. Protein unfolding can be caused by a variety of driving forces induced in different ways: increased temperature or pressure, change of solvent composition, or protein amino acid mutation. The stability and unfolding of four different proteins (bovine pancreatic trypsin inhibitor, hen egg white lysozyme, the surfactant protein C and the DNA-binding domain of the 434 repressor) have been studied by applying the afore-mentioned driving forces and also to some artificial forces. The results give a picture of protein (in)stability and possible unfolding pathways, and are compared to experimental data where possible.
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PMID:Investigation of protein unfolding and stability by computer simulation. 777 Apr 86

We have investigated the effect of the v-Myc oncoprotein on gene expression in myelomonocytic cells. We find that v-Myc dramatically down-regulates the expression of myelomonocytic-specific genes, such as the chicken mim-1 and lysozyme genes, both of which are known targets for C/EBP transcription factors. We present evidence that Myc downregulates these genes by inhibiting the function of C/EBP transcription factors. Detailed examination of the inhibitory mechanism shows that amino-terminal sequences of v-Myc, but not its DNA-binding domain, are required for the suppression of C/EBP-dependent transactivation. Our findings identify a new function for Myc and reveal a novel mechanism by which Myc affects the expression of other genes.
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PMID:A novel function for Myc: inhibition of C/EBP-dependent gene activation. 869 70

Since the transcription factor Zfhep is expressed in somatotropes and binds the rat growth hormone (rGH) gene T3-response element (TRE), we investigated whether Zfhep regulates the response of this gene to T3. In cotransfection experiments, Zfhep did not regulate the native rGH promoter in the absence of T3. However, Zfhep repressed T3-mediated activation significantly in either GH(3) or JEG-3 cells. Up to 70% repression was mediated through the rGH TRE in a heterologous promoter (thymidine kinase), but was not observed with the idealized DR4 or chicken lysozyme F2 TREs. Zfhep apparently does not repress T3-mediated activation simply by competition for binding to DNA since the C-terminal DNA-binding domain of Zfhep (which is sufficient for DNA-binding) is not sufficient for repression and since cotransfection of excess thyroid hormone receptor (TR) did not prevent repression by Zfhep. These data indicate that the rGH TRE is a composite element that can integrate Zfhep and T3 regulation.
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PMID:T3-activation of the rat growth hormone gene is inhibited by a zinc finger/homeodomain protein. 1147 47

Potential redundancy among members of the CCAAT/enhancer-binding protein (C/EBP) family in myeloid cells is indicated by the ability of C/EBPbeta to replace C/EBPalpha in vivo, by the expression of granulocyte colony-stimulating factor receptor (G-CSFR) on C/EBPalpha(-/-) cell lines, and by our finding that as with C/EBPalpha-estrogen receptor (C/EBPalpha-ER), either C/EBPbeta-ER or C/EBPdelta-ER can induce terminal granulopoiesis in 32D cl3 cells. To assess the consequences of globally inhibiting C/EBPs, we employed KalphaER, containing a Kruppel-associated box (KRAB) transrepression domain, the C/EBPalpha DNA-binding domain, and an ER ligand-binding domain. C/EBPs have a common DNA-binding consensus, and activation of KalphaER repressed transactivation by endogenous C/EBPs 50-fold and reduced endogenous G-CSFR expression. In 32D cl3 cells coexpressing exogenous G-CSFR, activation of KalphaER prevented and even reversed myeloperoxidase, lysozyme, lactoferrin, and C/EBPepsilon RNA induction by G-CSF. In contrast, induction of PU.1 and CD11b, a gene regulated by PU.1 but not by C/EBPs, was unaffected. A KalphaER variant incapable of binding DNA owing to an altered leucine zipper did not affect 32D cl3 differentiation. Transduction of KalphaER into murine hematopoietic progenitor cells suppressed the formation of granulocyte colony-forming units, even in cytokines that enable C/EBPalpha(-/-) progenitors to differentiate into neutrophils. The formation of macrophage and of granulocyte-macrophage colony-forming units were also inhibited, but erythroid burst-forming units grew normally. Thus, in 32D cl3 cells and perhaps normal progenitors, C/EBPs are required for granulopoiesis beyond their ability to induce receptors for G-CSF and other cytokines. One requisite activity may be activation of the C/EBPepsilon gene by C/EBPalpha, as either C/EBPalpha-ER or C/EBPbeta-ER rapidly elevated C/EBPepsilon RNA in 32D cl3 cells in the presence of cycloheximide but not actinomycin D.
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PMID:CCAAT/enhancer-binding proteins are required for granulopoiesis independent of their induction of the granulocyte colony-stimulating factor receptor. 1192 66

Interferon regulatory factor-8 (IRF-8)/interferon consensus sequence-binding protein (ICSBP) is a transcription factor that controls myeloid-cell development. Microarray gene expression analysis of Irf-8-/- myeloid progenitor cells expressing an IRF-8/estrogen receptor chimera (which differentiate into macrophages after addition of estradiol) was used to identify 69 genes altered by IRF-8 during early differentiation (62 up-regulated and 7 down-regulated). Among them, 4 lysosomal/endosomal enzyme-related genes (cystatin C, cathepsin C, lysozyme, and prosaposin) did not require de novo protein synthesis for induction, suggesting that they were direct targets of IRF-8. We developed a reporter assay system employing a self-inactivating retrovirus and analyzed the cystatin C and cathepsin C promoters. We found that a unique cis element mediates IRF-8-induced activation of both promoters. Similar elements were also found in other IRF-8 target genes with a consensus sequence (GAAANN[N]GGAA) comprising a core IRF-binding motif and an Ets-binding motif; this sequence is similar but distinct from the previously reported Ets/IRF composite element. Chromatin immunoprecipitation assays demonstrated that IRF-8 and the PU.1 Ets transcription factor bind to this element in vivo. Collectively, these data indicate that IRF-8 stimulates transcription of target genes through a novel cis element to specify macrophage differentiation.
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PMID:Identification of target genes and a unique cis element regulated by IRF-8 in developing macrophages. 1594 94

The oncoprotein v-Myb of avian myeloblastosis virus (AMV) transforms myelomonocytic cells by deregulating specific target genes. Previous work has shown that the oncogenic potential of v-Myb was activated by truncation of N- and C-terminal sequences of c-Myb and was further increased by amino acid substitutions in the DNA-binding domain and other parts of the protein. We have analyzed the activation of the chicken lysozyme gene which is strongly activated by c-Myb but not by its oncogenic counterpart v-Myb. We report that Myb acts on two different cis-regulatory elements, the promoter and an enhancer located upstream of the gene. Interestingly, the activation of the enhancer was abolished by the oncogenic amino acid substitutions. We demonstrated that a single Myb-binding site is responsible for the activation of the lysozyme enhancer by Myb and showed that the v-Myb protein of AMV was unable to bind to this site. Our data demonstrate for the first time that oncogenic activation of Myb alters its DNA-binding specificity at a physiological Myb target gene.
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PMID:Oncogenic point mutations in the Myb DNA-binding domain alter the DNA-binding properties of Myb at a physiological target gene. 1795 53