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1.
Elife ; 72018 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-30109982

RESUMO

The cohesin ring complex is required for numerous chromosomal transactions including sister chromatid cohesion, DNA damage repair and transcriptional regulation. How cohesin engages its chromatin substrate has remained an unresolved question. We show here, by determining a crystal structure of the budding yeast cohesin HEAT-repeat subunit Scc3 bound to a fragment of the Scc1 kleisin subunit and DNA, that Scc3 and Scc1 form a composite DNA interaction module. The Scc3-Scc1 subcomplex engages double-stranded DNA through a conserved, positively charged surface. We demonstrate that this conserved domain is required for DNA binding by Scc3-Scc1 in vitro, as well as for the enrichment of cohesin on chromosomes and for cell viability. These findings suggest that the Scc3-Scc1 DNA-binding interface plays a central role in the recruitment of cohesin complexes to chromosomes and therefore for cohesin to faithfully execute its functions during cell division.


Assuntos
Proteínas de Ciclo Celular/genética , Cromatina/genética , Proteínas Cromossômicas não Histona/genética , Cromossomos/genética , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Ciclo Celular/administração & dosagem , Proteínas de Ciclo Celular/química , Divisão Celular/genética , Cromatina/química , Proteínas Cromossômicas não Histona/administração & dosagem , Proteínas Cromossômicas não Histona/química , Cromossomos/química , DNA/química , DNA/genética , Dano ao DNA/genética , Reparo do DNA/genética , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Complexos Multiproteicos , Proteínas de Saccharomyces cerevisiae/química , Coesinas
2.
Neurobiol Aging ; 29(9): 1348-58, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17433504

RESUMO

The activity of protein phosphatase-2A (PP-2A) is significantly suppressed in the brain of Alzheimer's disease (AD) patients, but the mechanism is not understood. Here, we found an in vivo association of glycogen synthase kinase 3beta (GSK-3beta) with inhibitor-2 of PP-2A (I(2)(PP-2A)). The activation of GSK-3 resulted in accumulation of I(2)(PP-2A) with concomitant suppression of PP-2A activity and increases of tau phosphorylation in HEK293, N2a and PC12 cells, while inhibition of GSK-3 caused decreases of I(2)(PP-2A) with increased PP-2A activity and decreased tau phosphorylation. A positive correlation between GSK-3beta and I(2)(PP-2A) (R=0.9158) and a negative correlation between GSK-3beta and PP-2A (R=-0.9166) were detected. GSK-3 activation did not affect I(2)(PP-2A) mRNA level, while it increased the mRNA level of a heterogeneous ribonucleoprotein A18 (hnRNP A18). The activation of GSK-3 increased the expression and the activity of proteasome system. It suggests that activation of GSK-3 inhibits PP-2A through up-regulation of I(2)(PP-2A) with hnRNP A18-involved mechanism.


Assuntos
Proteínas Cromossômicas não Histona/administração & dosagem , Quinase 3 da Glicogênio Sintase/metabolismo , Neurônios/metabolismo , Proteína Fosfatase 2/metabolismo , Transdução de Sinais/fisiologia , Fatores de Transcrição/administração & dosagem , Linhagem Celular , Proteínas de Ligação a DNA , Glicogênio Sintase Quinase 3 beta , Chaperonas de Histonas , Humanos , Neurônios/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
3.
J Immunol ; 165(4): 2263-70, 2000 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-10925315

RESUMO

The heavy metal mercury elicits a genetically restricted autoantibody response in mice that targets the nucleolar autoantigen fibrillarin. HgCl2-induced cell death of macrophages resulted in the proteolytic cleavage of fibrillarin. A prominent feature of mercury-induced cell death was the generation of a 19-kDa fragment of fibrillarin that was not found following apoptotic or nonapoptotic cell death induced by stimuli other than mercury. Proteolysis of fibrillarin lacking cysteines, and therefore unable to bind mercury, also produced the 19-kDa fragment, suggesting that a mercury-fibrillarin interaction was not necessary for the unique cleavage pattern of this self-Ag. In contrast to immunization with full-length fibrillarin, the 19-kDa fragment produced anti-fibrillarin Abs with some of the properties of the HgCl2-induced anti-fibrillarin response. We propose that cell death following exposure to an autoimmunity-inducing xenobiotic can lead to the generation of novel protein fragments that may serve as sources of antigenic determinants for self-reactive T lymphocytes.


Assuntos
Apoptose/efeitos dos fármacos , Apoptose/imunologia , Autoantígenos/metabolismo , Fragmentos de Peptídeos/biossíntese , Fragmentos de Peptídeos/imunologia , Xenobióticos/farmacologia , Animais , Apoptose/genética , Autoanticorpos/biossíntese , Autoantígenos/administração & dosagem , Autoantígenos/genética , Autoantígenos/imunologia , Linhagem Celular , Proteínas Cromossômicas não Histona/administração & dosagem , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/imunologia , Proteínas Cromossômicas não Histona/metabolismo , Hidrólise , Injeções Subcutâneas , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Cloreto de Mercúrio/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Peso Molecular , Mutagênese Sítio-Dirigida , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/genética
4.
Ontogenez ; 12(4): 418-21, 1981.
Artigo em Russo | MEDLINE | ID: mdl-7306301

RESUMO

Polyethylene glycol was applied to microinject two exogenous proteins: bovine serum albumin and non-histone protein derived from mouse spleen chromatin, into the mouse L-cells. The effectiveness of fusion of mammal (human, in the given case) erythrocytes in which hemoglobin is substituted for the protein under study was shown to be higher than when Sendai virus was used. The microinjected proteins preserve their specificity to subcellular structures.


Assuntos
Proteínas Cromossômicas não Histona/administração & dosagem , Células L/efeitos dos fármacos , Microinjeções/métodos , Polietilenoglicóis/farmacologia , Soroalbumina Bovina/administração & dosagem , Animais , Bovinos , Fusão Celular/efeitos dos fármacos , Células Cultivadas , Eritrócitos/efeitos dos fármacos , Humanos , Camundongos
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