Restoration of the DNA binding activity of estrogen receptor in MRL-lpr/lpr mice by a polyamine biosynthesis inhibitor

1991 ◽  
Vol 34 (1) ◽  
pp. 55-62 ◽  
Author(s):  
Thresia Thomas ◽  
Uma B. Gunnia ◽  
James R. Seibold ◽  
T. J. Thomas
Keyword(s):  
Estrogen Receptor ◽  
Dna Binding ◽  
Binding Activity ◽  
Polyamine Biosynthesis ◽  
Biosynthesis Inhibitor ◽  
Dna Binding Activity

A 22-amino-acid peptide restores DNA-binding activity to dimerization-defective mutants of the estrogen receptor

1990 ◽  
Vol 10 (10) ◽  
pp. 5529-5531
Author(s):  
J A Lees ◽  
S E Fawell ◽  
R White ◽  
M G Parker
Keyword(s):  
Estrogen Receptor ◽  
Amino Acid ◽  
Dna Binding ◽  
Binding Activity ◽  
Binding Domain ◽  
Amino Acid Peptide ◽  
High Affinity ◽  
Dna Binding Activity ◽  
Point Mutagenesis ◽  
Hormone Binding Domain

We have identified residues within the estrogen receptor that are required for dimerization and high-affinity DNA binding. A 22-amino-acid peptide encompassing these residues was sufficient to restore DNA-binding activity to a mutant receptor lacking most of the hormone-binding domain. Point mutagenesis of the fusion protein confirmed that this sequence continued to mediate dimerization in a manner similar to that within the native receptor, although its position relative to the DNA-binding domain was appreciably altered.

scholarly journals A 22-amino-acid peptide restores DNA-binding activity to dimerization-defective mutants of the estrogen receptor.

1990 ◽  
Vol 10 (10) ◽  
pp. 5529-5531 ◽  
Author(s):  
J A Lees ◽  
S E Fawell ◽  
R White ◽  
M G Parker
Keyword(s):  
Estrogen Receptor ◽  
Amino Acid ◽  
Dna Binding ◽  
Binding Activity ◽  
Binding Domain ◽  
Amino Acid Peptide ◽  
High Affinity ◽  
Dna Binding Activity ◽  
Point Mutagenesis ◽  
Hormone Binding Domain

We have identified residues within the estrogen receptor that are required for dimerization and high-affinity DNA binding. A 22-amino-acid peptide encompassing these residues was sufficient to restore DNA-binding activity to a mutant receptor lacking most of the hormone-binding domain. Point mutagenesis of the fusion protein confirmed that this sequence continued to mediate dimerization in a manner similar to that within the native receptor, although its position relative to the DNA-binding domain was appreciably altered.

scholarly journals Structure of the p53/RNA polymerase II assembly

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Shu-Hao Liou ◽  
Sameer K. Singh ◽  
Robert H. Singer ◽  
Robert A. Coleman ◽  
Wei-Li Liu
Keyword(s):  
Dna Binding ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Conformational Changes ◽  
P53 Protein ◽  
Binding Activity ◽  
Transactivation Domain ◽  
Pol Ii ◽  
Dna Binding Activity ◽  
Regulated Gene Expression

AbstractThe tumor suppressor p53 protein activates expression of a vast gene network in response to stress stimuli for cellular integrity. The molecular mechanism underlying how p53 targets RNA polymerase II (Pol II) to regulate transcription remains unclear. To elucidate the p53/Pol II interaction, we have determined a 4.6 Å resolution structure of the human p53/Pol II assembly via single particle cryo-electron microscopy. Our structure reveals that p53’s DNA binding domain targets the upstream DNA binding site within Pol II. This association introduces conformational changes of the Pol II clamp into a further-closed state. A cavity was identified between p53 and Pol II that could possibly host DNA. The transactivation domain of p53 binds the surface of Pol II’s jaw that contacts downstream DNA. These findings suggest that p53’s functional domains directly regulate DNA binding activity of Pol II to mediate transcription, thereby providing insights into p53-regulated gene expression.

scholarly journals Abundance Changes of the Response Regulator RcaC Require Specific Aspartate and Histidine Residues and Are Necessary for Normal Light Color Responsiveness

2008 ◽  
Vol 190 (21) ◽  
pp. 7241-7250 ◽  
Author(s):  
Lina Li ◽  
David M. Kehoe
Keyword(s):  
Dna Binding ◽  
Dynamic Range ◽  
Response Regulator ◽  
Red Light ◽  
Green Light ◽  
Binding Activity ◽  
Transcriptional Responses ◽  
Dna Binding Activity ◽  
Normal Light ◽  
Light Color

ABSTRACT RcaC is a large, complex response regulator that controls transcriptional responses to changes in ambient light color in the cyanobacterium Fremyella diplosiphon. The regulation of RcaC activity has been shown previously to require aspartate 51 and histidine 316, which appear to be phosphorylation sites that control the DNA binding activity of RcaC. All available data suggest that during growth in red light, RcaC is phosphorylated and has relatively high DNA binding activity, while during growth in green light RcaC is not phosphorylated and has less DNA binding activity. RcaC has also been found to be approximately sixfold more abundant in red light than in green light. Here we demonstrate that the light-controlled abundance changes of RcaC are necessary, but not sufficient, to direct normal light color responses. RcaC abundance changes are regulated at both the RNA and protein levels. The RcaC protein is significantly less stable in green light than in red light, suggesting that the abundance of this response regulator is controlled at least in part by light color-dependent proteolysis. We provide evidence that the regulation of RcaC abundance does not depend on any RcaC-controlled process but rather depends on the presence of the aspartate 51 and histidine 316 residues that have previously been shown to control the activity of this protein. We propose that the combination of RcaC abundance changes and modification of RcaC by phosphorylation may be necessary to provide the dynamic range required for transcriptional control of RcaC-regulated genes.

Differential use of SCL/TAL-1 DNA-binding domain in developmental hematopoiesis

Blood ◽  
2008 ◽  
Vol 112 (4) ◽  
pp. 1056-1067 ◽  
Author(s):  
Mira T. Kassouf ◽  
Hedia Chagraoui ◽  
Paresh Vyas ◽  
Catherine Porcher
Keyword(s):  
Dna Binding ◽  
Molecular Mechanisms ◽  
Binding Activity ◽  
Hematopoietic Stem ◽  
Helix Loop Helix ◽  
Experimental Systems ◽  
Dna Binding Activity ◽  
Independent Functions

Abstract Dissecting the molecular mechanisms used by developmental regulators is essential to understand tissue specification/differentiation. SCL/TAL-1 is a basic helix-loop-helix transcription factor absolutely critical for hematopoietic stem/progenitor cell specification and lineage maturation. Using in vitro and forced expression experimental systems, we previously suggested that SCL might have DNA-binding–independent functions. Here, to assess the requirements for SCL DNA-binding activity in vivo, we examined hematopoietic development in mice carrying a germline DNA-binding mutation. Remarkably, in contrast to complete absence of hematopoiesis and early lethality in scl-null embryos, specification of hematopoietic cells occurred in homozygous mutant embryos, indicating that direct DNA binding is dispensable for this process. Lethality was forestalled to later in development, although some mice survived to adulthood. Anemia was documented throughout development and in adulthood. Cellular and molecular studies showed requirements for SCL direct DNA binding in red cell maturation and indicated that scl expression is positively autoregulated in terminally differentiating erythroid cells. Thus, different mechanisms of SCL's action predominate depending on the developmental/cellular context: indirect DNA binding activities and/or sequestration of other nuclear regulators are sufficient in specification processes, whereas direct DNA binding functions with transcriptional autoregulation are critically required in terminal maturation processes.

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