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| Registros recuperados: 15 | |
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| Michael E. Baker. |
| 11[beta]-hydroxysteroid dehydrogenase type-2 (11[beta]-HSD2) regulates the local concentration of cortisol that can activate the glucocorticoid receptor and mineralocorticoid receptor, as well as the concentration of 11-keto-testosterone, the active androgen in fish. Similarly, 17[beta]-HSD2 regulates the levels of testosterone and estradiol that activate the androgen receptor and estrogen receptor, respectively. Interestingly, although human 11[beta]-HSD2 and 17[beta]-HSD2 act at different positions on different steroids, these enzymes are paralogs. Despite the physiological importance of 11[beta]-HSD2 and 17[beta]-HSD2, details of their origins and divergence from a common ancestor are not known. An opportunity to understand their evolution is... |
| Tipo: Manuscript |
Palavras-chave: Cancer; Developmental Biology; Pharmacology; Bioinformatics; Evolutionary Biology. |
| Ano: 2010 |
URL: http://precedings.nature.com/documents/4649/version/1 |
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| Michael E. Baker; David J. Chang. |
| The origins of signaling by vertebrate steroids are not fully understood. An important advance was the report that an estrogen-binding steroid receptor [SR] is present in amphioxus, a basal chordate with a similar body plan as vertebrates. To investigate the evolution of estrogen binding to steroid receptors, we constructed a 3D model of amphioxus SR complexed with estradiol. This 3D model indicates that although the SR is activated by estradiol, some interactions between estradiol and human ER[alpha] are not conserved in the SR, which can explain the low affinity of estradiol for the SR. These differences between the SR and ER[alpha] in the steroid-binding domain are sufficient to suggest that another steroid is the physiological regulator of the SR.... |
| Tipo: Manuscript |
Palavras-chave: Cancer; Developmental Biology; Bioinformatics; Evolutionary Biology. |
| Ano: 2009 |
URL: http://precedings.nature.com/documents/3316/version/1 |
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| Michael E. Baker; David J. Chang; Charlie Chandsawangbhuwana. |
| Lamprey, a basal vertebrate, contains orthologs of the estrogen receptor (ER), progesterone receptor and corticoid receptor. A perplexing property of lamprey is that 15[alpha]-hydroxy-steroids are active steroids. For example, 15[alpha]-hydroxy-estradiol [15[alpha]-OH-E2] is the estrogen, instead of estradiol (E2). To investigate how 15[alpha]-OH-E2 binds lamprey ER, we constructed a 3D model of the lamprey ER with E2 and 15[alpha]-OH-E2. Our 3D model shows that S[delta] on Met-409 can form a hydrogen bond with the 15[alpha]-hydroxyl on 15[alpha]-OH-E2. In human ER[alpha], the corresponding residue Ile-424 has a van der Waals contact with 15[alpha]-OH-E2. BLAST analysis of GenBank indicates that among vertebrate ERs, only lamprey ER contains a... |
| Tipo: Manuscript |
Palavras-chave: Developmental Biology; Ecology; Earth & Environment. |
| Ano: 2009 |
URL: http://precedings.nature.com/documents/2768/version/1 |
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| Michael E. Baker; Kayla Y. Uh; Paiyuam Asnaashari. |
| The serum of Atlantic sea lamprey, a basal vertebrate, contains two corticosteroids, 11-deoxycortisol and deoxycorticosterone. Only 11-deoxycortisol has high affinity [Kd~3 nM] for the corticoid receptor [CR] in lamprey gill cytosol. To investigate the binding of 11-deoxycortisol to the CR, we constructed 3D models of lamprey CR complexed with 11-deoxycortisol and deoxycorticosterone. These 3D models reveal that Leu-220 and Met-299 in lamprey CR have contacts with the 17[alpha]-hydroxyl on 11-deoxycortisol. Lamprey CR is the ancestor of the mineralocorticoid receptor [MR] and glucocorticoid receptor [GR]. Unlike human MR and human GR, the 3D model of lamprey CR finds a van der Waals contact between Cys-227 in helix 3 and Met-264 in helix 5. Mutant... |
| Tipo: Manuscript |
Palavras-chave: Cancer; Developmental Biology; Pharmacology; Bioinformatics; Evolutionary Biology. |
| Ano: 2011 |
URL: http://precedings.nature.com/documents/6216/version/1 |
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| Michael E. Baker. |
| A key regulator of glucocorticoid action is 11[beta]-hydroxysteroid dehydrogenase type-1 (11[beta]-HSD1), which catalyzes the conversion of cortisone to cortisol, the biologically active glucocorticoid. 11[beta]-HSD1 is a paralog of 11[beta]-HSD3, whose physiological function remains unclear. As reported here, 11[beta]-HSD3 has orthologs in sea urchin, amphioxus and Ciona, while 11[beta]-HSD1 first appears in sharks. Thus, 11[beta]HSD3 arose before the evolution of glucocorticoid signaling, suggesting different ancestral function(s) for 11[beta]-HSD3. Four perplexing findings arise from this evolutionary analysis: 1) 11[beta]-HSD1 is not present in a ray-finned fish genome, 2) zebrafish and fathead minnow contain two isoforms of 11[beta]-HSD3; 3)... |
| Tipo: Manuscript |
Palavras-chave: Developmental Biology; Ecology; Genetics & Genomics; Earth & Environment; Evolutionary Biology. |
| Ano: 2010 |
URL: http://precedings.nature.com/documents/4296/version/1 |
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| Michael E. Baker. |
| In the last decade, there has been important progress in understanding the origins and evolution of receptors for adrenal steroids (aldosterone, cortisol) and sex steroids (estradiol, progesterone, testosterone) due to the sequencing of genomes from animals that are at key sites in vertebrate evolution. Although the estrogen receptor [ER] appears to be the ancestral vertebrate steroid receptor and estradiol [E2] is the physiological ligand for vertebrate ERs, the identity of the ancestral ligand(s) for the ER remains unknown. Here, using an analysis of crystal structures of human ER[alpha] with E2 and other chemicals and 3D models of human ER[alpha] with 27-hydroxycholesterol and 5-androsten-3[beta],17[beta]-diol, we propose that one or more [DELTA]5... |
| Tipo: Manuscript |
Palavras-chave: Cancer; Developmental Biology; Ecology; Genetics & Genomics; Pharmacology; Bioinformatics; Earth & Environment; Evolutionary Biology. |
| Ano: 2011 |
URL: http://precedings.nature.com/documents/5777/version/1 |
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| Michael E. Baker; Charlie Chandsawangbhuwana. |
| *Background.* The origins of steroid-dependent regulation of the vertebrate estrogen receptor (ER) are poorly understood. Genes with statistically significant sequence similarity to vertebrate ERs have been found in lamprey, a basal vertebrate, and amphioxus, a basal chordate. Motif analysis of these sequences provides an opportunity to investigate early events in the evolution of the ER.
*Results.* We used artificial intelligence-based software to construct twelve motifs specific to the estrogen-binding domain of ER[alpha] and ER[beta] in land vertebrates and teleosts. We mapped these ER-specific motifs onto the sequences of lamprey, amphioxus, invertebrate and selected vertebrate ERs and amphioxus, Ciona and human estrogen-related... |
| Tipo: Manuscript |
Palavras-chave: Cancer; Developmental Biology; Ecology; Evolutionary Biology. |
| Ano: 2008 |
URL: http://precedings.nature.com/documents/1542/version/2 |
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| Michael E. Baker; Charlie Chandsawangbhuwana. |
| *Background.* The origins of steroid-dependent regulation of the vertebrate estrogen receptor (ER) are poorly understood. Genes with statistically significant sequence similarity to vertebrate ERs have been found in lamprey, a basal vertebrate, and amphioxus, a basal chordate. Motif analysis of these sequences provides an opportunity to investigate early events in the evolution of the ER.
*Results.* We used artificial intelligence-based software to construct twelve motifs specific to the estrogen-binding domain of ER[alpha] and ER[beta] in land vertebrates and teleosts. We mapped these ER-specific motifs onto the sequences of lamprey, amphioxus, invertebrate and selected vertebrate ERs and amphioxus and human estrogen-related receptor... |
| Tipo: Manuscript |
Palavras-chave: Cancer; Developmental Biology; Ecology; Bioinformatics. |
| Ano: 2008 |
URL: http://precedings.nature.com/documents/1542/version/1 |
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| Michael E. Baker. |
| Recent sequencing of amphioxus and sea urchin genomes has provided important data for understanding the origins of enzymes that synthesize adrenal and sex steroids and the receptors that mediate physiological response to these vertebrate steroids. Phylogenetic analyses reveal that CYP11A and CYP19, which are involved in the synthesis of adrenal and sex steroids, first appear in the common ancestor of amphioxus and vertebrates. This correlates with recent evidence for the first appearance in amphioxus of receptors with close similarity to vertebrate steroid receptors. Other CYP450 enzymes involved in steroid synthesis can be traced back to invertebrates, in which they have at least two functions: detoxifying xenobiotics and catalyzing the synthesis of... |
| Tipo: Manuscript |
Palavras-chave: Developmental Biology; Bioinformatics; Evolutionary Biology. |
| Ano: 2010 |
URL: http://precedings.nature.com/documents/4674/version/1 |
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| Michael E. Baker. |
| Although, as their names imply, estrogen receptors [ERs] and estrogen-related receptors [ERRs] are related transcription factors, their evolutionary relationships to each other are not fully understood. To elucidate the origins and evolution of ERs and ERRs, we searched for their orthologs in the recently sequenced genome of _Trichoplax_, the simplest known animal, and in the genomes of three lophotrochozoans: _Capitella_, an annelid worm, _Helobdella robusta_, a leech, and _Lottia gigantea_, a snail. BLAST searches found an ERR in _Trichoplax_, but no ER. BLAST searches also found ERRs in all three lophotrochozoans and invertebrate-like ERs in _Capitella_ and _Lottia_, but not in _Helobdella_. Unexpectedly we find that the _Capitella_ ER sequence is... |
| Tipo: Manuscript |
Palavras-chave: Developmental Biology; Ecology; Evolutionary Biology. |
| Ano: 2008 |
URL: http://precedings.nature.com/documents/2170/version/1 |
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| Michael E. Baker. |
| Although, as their names imply, vertebrate and invertebrate estrogen receptors [ERs] and estrogen-related receptors [ERRs] are related transcription factors, their evolutionary relationships to each other are not fully understood. We searched recently sequenced genome of _Trichoplax_, the simplest known animal, and genomes from three lophotrochozoans: _Capitella_, a worm, _Helobdella robusta_, a leech, and _Lottia gigantea_, a snail, to elucidate the origins and evolution of ERs and ERRs. BLAST found an ERR in _Trichoplax_, but no ER. BLAST searches of the lophotrochozaons found ERRs in all three and invertebrate ERs in _Capitella_ and _Lottia_, but not in _Helobdella_. These database searches and a phylogenetic analyses indicate that invertebrate ERs... |
| Tipo: Manuscript |
Palavras-chave: Developmental Biology; Ecology; Evolutionary Biology. |
| Ano: 2008 |
URL: http://precedings.nature.com/documents/1863/version/1 |
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| Registros recuperados: 15 | |
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