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Lois R. Manning James M. Manning 《Protein science : a publication of the Protein Society》2018,27(3):662-671
The effect of phosphorylation on the basicities of amines in histone H3 peptides and their acetylation kinetics is probed with a mild chemical acetylating agent. Phosphorylation of Ser‐10 lowers the rate of chemical acetylation of Lys‐9, Lys‐14, and Lys‐18 by methyl acetyl phosphate in that order consistent with a higher pKa of these Lys residues induced by phosphorylation; basicities increase up to 3 pKa units as a function of distance from Ser‐10 phosphate. Enzymic acetylation of Lys residues with high pKa values in nucleosomes is also expected to be enhanced by phosphorylation, consistent with the known mechanism involving binding of protonated amines to N‐acetyltransferases; fetal hemoglobin has a related linkage of increased basicity at a specific site, its acetylation, and a resulting decrease in subunit interaction strength. In the absence of a phosphate on Ser‐10, the amines of Lys‐9, Lys‐14, and Lys‐18 have lowered pKa values. Chemical acetylation of glycine and glycinamide have analogous kinetic profiles to the histone peptides but the phosphate inductive effect in histone H3 is more potent since the linkage between phosphorylation and acetylation is propagated with a range extending 9–10 amino acids in either direction from the phosphorylation site enhancing protonation of amino groups. We conclude that lysine amine basicities in histone tails are not static but inducible and variable due to a dynamic and immediate interaction between phosphorylation/acetylation that may contribute to inactive heterochromatin by compaction through such Ser phosphate–Lys amine electrostatic interactions and their relaxation by acetylation in euchromatin. 相似文献
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真核生物核小体组蛋白修饰引起染色质重塑(Chromatin remodeling)是表观遗传的重要调控机制.乙酰化修饰(Acetylation modification)是其中一种重要的方式.组蛋白乙酰化修饰位点集中在各种组蛋白N末端赖氨酸残基上.细胞内存在功能拮抗的多种乙酰基转移酶和去乙酰化酶,二者相互竞争,共同调节组蛋白的乙酰化状态,通过影响核小体结构的致密性,并在多种效应分子的参与下,实现对基因的表达调控.以真核模式生物酿酒酵母(Saccharomyces cerevisiae)为对象,综述乙酰基转移酶和去乙酰化酶的种类、作用特点以及其基因调控的分子机制等方面的最新研究进展. 相似文献
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Src-suppressed C kinase substrate (SSeCKS) plays a role in membrane-cytoskeletal remodeling to regulate mitogenesis, cell differentiation,
and motility. Previous study showed that lipopolysaccharide (LPS) induced a selective and strong expression of SSeCKS in the
vascular endothelial cells of lung. Here we show that LPS stimulation elevated expression of SSeCKS mRNA and protein in Rat
pulmonary microvascular endothelial cell (RPMVEC). LPS potentiated SSeCKS phosphorylation in a time- and dose-dependent manner,
and partly induced translocation of SSeCKS from the cytosol to the membrane after LPS challenge. The PKC inhibitor, Calphostin
C, significantly decreased LPS-induced phosphorylation of SSeCKS, inhibited SSeCKS translocation and actin cytoskeleton reorganization
after LPS challenge, suggesting that PKC may play a role in LPS-induced SSeCKS translocation and actin rearrangement. We conclude
that SSeCKS is located downstream of PKC and that SSeCKS and PKC are both necessary for LPS-induced stress fiber formation.
Chun Cheng and Haiou Liu are contributed equally to this work. 相似文献
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Science China Life Sciences - 相似文献
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Complexities of gene regulation by cAMP 总被引:9,自引:0,他引:9
M Karin 《Trends in genetics : TIG》1989,5(3):65-67
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A role for the Cr2 gene in modifying autoantibody production in systemic lupus erythematosus 总被引:3,自引:0,他引:3
Wu X Jiang N Deppong C Singh J Dolecki G Mao D Morel L Molina HD 《Journal of immunology (Baltimore, Md. : 1950)》2002,169(3):1587-1592
Systemic lupus erythematosus is an autoimmune disease characterized by autoantibody production against nuclear Ags. Recent studies suggest that the Cr2 gene, which encodes for complement receptor (CR)1 and CR2, is important in disease susceptibility. Because the precise disease phenotype related to this gene, in isolation or in relation to other genetic loci, is not known, we analyzed C57BL/6 mice with a targeted mutation in Cr2 (C57BL/6.Cr2(-/-)) with or without a concomitant mutation in Fas (C57BL/6.lpr Cr2(-/-)). The Cr2(null) mutation in a C57BL/6.lpr background markedly increases the serum concentrations of IgG1 and IgG2b and the levels of antinuclear and anti-dsDNA Abs as compared with C57BL/6.lpr controls. There is also a trend for higher concentrations of IgG2a and IgG3. In contrast, isolated deficiencies in either these CRs or Fas have a limited effect in the production of anti-dsDNA Abs. Moreover, the Cr2(null) mutation does not affect other disease manifestations. These findings demonstrate that abnormalities in CR1 and CR2 may be linked to the production of autoantibodies by modifying the effect of other systemic lupus erythematosus susceptibility genes. Phenotypic expression of other disease manifestations need additional Cr2-independent genetic factors. 相似文献
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Ramos-Jiliberto R 《Theoretical population biology》2003,64(2):221-231
The effect of antipredator behavior on the dynamics of a resource-consumer model was analyzed in relation to the magnitude of associated costs, and the strength of density-dependence. For this purpose, I present a deterministic continuous resource-consumer model that exhibits biomass conversion, structural homogeneity, and competition for renewable and fixed resources as separate processes. Antipredator behavior is incorporated as an inducible response to consumer density, and has metabolic and feeding costs. By means of numerical methods, I show: (1) that antipredator behavior is stabilizing for certain parameter ranges, where other stabilizing forces do not dominate the dynamics; (2) intraspecific competition for both fixed and renewable resources have a stabilizing role; (3) metabolic cost is always stabilizing, and feeding cost can be stabilizing or destabilizing, depending on the relative strength of the two competition forces. 相似文献
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Regulation of hormone-induced histone hyperacetylation and gene activation via acetylation of an acetylase. 总被引:50,自引:0,他引:50
Nuclear receptors have been postulated to regulate gene expression via their association with histone acetylase (HAT) or deacetylase complexes. We report that hormone induces dramatic hyperacetylation at endogenous target genes through the HAT activity of p300/CBP. Unexpectedly, this hyperacetylation is transient and coincides with attenuation of hormone-induced gene activation. In exploring the underlying mechanism, we found that the acetylase ACTR can be acetylated by p300/CBP. The acetylation neutralizes the positive charges of two lysine residues adjacent to the core LXXLL motif and disrupts the association of HAT coactivator complexes with promoter-bound estrogen receptors. These results provide strong in vivo evidence that histone acetylation plays a key role in hormone-induced gene activation and define cofactor acetylation as a novel regulatory mechanism in hormonal signaling. 相似文献
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Histone acetylation in gene regulation. 总被引:3,自引:0,他引:3
Loredana Verdone Eleonora Agricola Micaela Caserta Ernesto Di Mauro 《Briefings in Functional Genomics and Prot》2006,5(3):209-221
Genetic information is packaged in the highly dynamic nucleoprotein structure called chromatin. Many biological processes are regulated via post-translational modifications of key proteins. Acetylation of lysine residues at the N-terminal histone tails is one of the most studied covalent modifications influencing gene regulation in eukaryotic cells. This review focuses on the role of enzymes involved in controlling both histone and non-histone proteins acetylation levels in the cell, with particular emphasis on their effects on cancer. 相似文献
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Isolation and structural characterization of the human 4F2 heavy-chain gene, an inducible gene involved in T-lymphocyte activation. 总被引:10,自引:3,他引:7 下载免费PDF全文
K M Gottesdiener B A Karpinski T Lindsten J L Strominger N H Jones C B Thompson J M Leiden 《Molecular and cellular biology》1988,8(9):3809-3819