Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A high affinity calcium-binding protein has recently been purified from the adrenal medulla (Kuo, I.C.Y., and Coffee, C.J. (1976) J. Biol. Chem. 251, 1603-1609). This protein is closely related in its chemical and physical properties to troponin-C (TN-C) of muscle tissue. Further examination of the adrenal medulla protein indicates that the removal of calcium is accompanied by a marked change in the conformation. This change in structure is similar, if not identical, to the calcium-dependent conformational change which has been described for skeletal muscle TN-C (Murray, A.C., and Kay, C.M. (1972) Biochemistry 11, 2622). The far ultraviolet circular dichroism spectrum of native adrenal medulla calcium-binding protein (AM-CBP) shows characteristic helical ellipticity bands at 222 and 207 nm. The helical content, as estimated from these data, is between 40 and 45%. Removal of calcium is accompanied by a change in ellipticity which corresponds to a decrease from 40 to 20% in the helical content. The near-ultraviolet circular dichroism spectrum shows negative dichroic bands at 262 and 268 nm which are characteristic of phenylalanine. These bands are relatively insensitive to changes in the calcium ion concentration. Sedimentation velocity studies likewise are indicative of a calcium-dependent structural alteration. The sedimentation coefficient of the native protein was observed to be 1.89 S. Similar measurements performed in the presence of 3 mM ethylene glycol bis(beta-aminoethyl ether) N,N, N', N'-tetraacetic acid (EGTA) gave a sedimentation coefficient of 1.50 S. The molecular weight, as determined by sedimentation equilibrium studies, was 16,000 regardless of whether the measurements were made in the presence of CaCl2 or EGTA. From the elution properties of AM-CBP on Sephadex G-100, the Stokes radius was observed to be 19.8 A in the presence of calcium and 21.9 A in the presence of EGTA. All of these changes which were induced by the addition of EGTA were completely reversible by the readdition of excess CaCl2. These data suggest that the removal of calcium from AM-CBP is accompanied by a pronounced conformational change which occurs without a molecular weight change. The decreased sedimentation coefficient, the increased Stokes radius, and the reduced helical content, which are observed for the apoprotein, indicate that removal of calcium results in a transformation from a compact symmetrical structure to one that is less ordered and more asymmetrical.
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PMID:Bovine adrenal medulla troponin-C. Demonstration of a calcium-dependent conformational change. 97 71

Transcriptional activity of both ATF-1 and CREB is enhanced by protein phosphorylation. While enhancement has been attributed to an increase in binding affinity for a co-activator (CBP), induction of the DNA binding activity by phosphorylation is an open question. Using the Na,K-ATPase alpha1 subunit gene promoter, which has an asymmetrical ATF/CRE site, we analyzed the effect of phosphorylation on DNA binding activity of the ATF-1-CREB heterodimer. Dephosphorylation of the heterodimer in nuclear extracts reduced binding to the ATF/CRE site. Phosphorylation of ATF-1 at Ser63 enhanced its binding to the ATF/CRE site in both the homodimeric and heterodimeric forms. Transcription of the Na,K-ATPase alpha 1 subunit gene promoter was also stimulated by phosphorylated ATF-1 in vitro.
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PMID:Phosphorylation of ATF-1 enhances its DNA binding and transcription of the Na,K-ATPase alpha 1 subunit gene promoter. 901 41

The human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus that integrates randomly into the T-cell genome. Two long terminal repeats (LTRs) flank the integrated provirus. The upstream and downstream LTRs carry identical promoter sequences. Studies with other retroviruses suggest that the downstream promoter is silent and that RNA polymerases initiating at the upstream promoter proceed through the 3' LTR. In this study, we used the chromatin immunoprecipitation assay to compare the binding of transcription regulatory proteins at both the upstream and downstream promoters in HTLV-1-infected cell lines and adult T-cell leukemia-lymphoma cells. Unexpectedly, we detected a nearly equal distribution of activator (Tax, CREB, ATF-1, ATF-2, c-Fos, and c-Jun) and regulatory protein (CBP, p300, TAF(II)250, and polymerase II) binding at both the upstream and downstream promoters. Consistent with this observation, we found that the downstream promoter was transcriptionally active, suggesting that the two promoters are functionally equivalent. We also detected asymmetrical binding of histone deacetylases (HDAC-1, -2, and -3) at both promoters. All three HDACs strongly repressed Tax transactivation, and this repression correlated with displacement of Tax from the HTLV-1 promoter. These effects were reciprocal, as Tax expression reversed HDAC repression and displaced HDACs from the HTLV-1 promoter. These data suggest that HTLV-1 transcriptional regulation at both the 5' and 3' LTRs is mediated, in part, through the mutually exclusive binding of Tax and HDACs at the proviral promoters.
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PMID:Transcription regulatory complexes bind the human T-cell leukemia virus 5' and 3' long terminal repeats to control gene expression. 1522 16