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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
37
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pubmed:dateCreated |
2001-9-10
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pubmed:abstractText |
cGMP-phosphodiesterase (PDE) is the key effector in rod photoreceptor signal transduction. Mutations in the gene encoding its catalytic beta-subunit (beta-PDE) cause retinal degenerations leading to blindness. We report that the short -93 to +53 sequence in the upstream region of this gene is sufficient for beta-PDE transcription in both Y79 human retinoblastoma cells and Xenopus embryo heads maintained ex vivo. This sequence also functions as a minimal rod-specific promoter in transgenic Xenopus tadpoles. The Nrl transcription factor binds in vitro to the betaAp1/NRE regulatory element located within this region and transactivates it when overexpressed in nonretinal 293 embryonic kidney cells. We also found a G/C-rich activator element, beta/GC, important for promoter activity in Y79 retinoblastoma cells and Xenopus embryos. Both the ubiquitous Sp1 and the central nervous system-specific Sp4 transcription factors are expressed in retina and interact with this element in vitro. Electrophoretic mobilities of beta/GC-Y79 nuclear protein complexes are altered by antibodies against Sp1 and Sp4. Thus, our results implicate Nrl, Sp1, and Sp4 in transcriptional regulation of the rod-specific minimal beta-PDE promoter. We also conclude that Xenopus laevis is an efficient system for analyzing the human beta-PDE promoter and may be used to study other human retinal genes ex vivo and in vivo.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3',5'-Cyclic-GMP Phosphodiesterases,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic Nucleotide...,
http://linkedlifedata.com/resource/pubmed/chemical/IL11RA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-11 Receptor alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/PDE6B protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoric Diester Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-11,
http://linkedlifedata.com/resource/pubmed/chemical/SP4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Sp1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Sp4 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
14
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pubmed:volume |
276
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
34999-5007
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:11438531-3',5'-Cyclic-GMP Phosphodiesterases,
pubmed-meshheading:11438531-Animals,
pubmed-meshheading:11438531-Cyclic Nucleotide Phosphodiesterases, Type 6,
pubmed-meshheading:11438531-Female,
pubmed-meshheading:11438531-HeLa Cells,
pubmed-meshheading:11438531-Humans,
pubmed-meshheading:11438531-Interleukin-11 Receptor alpha Subunit,
pubmed-meshheading:11438531-Phosphoric Diester Hydrolases,
pubmed-meshheading:11438531-Promoter Regions, Genetic,
pubmed-meshheading:11438531-Receptors, Interleukin,
pubmed-meshheading:11438531-Receptors, Interleukin-11,
pubmed-meshheading:11438531-Response Elements,
pubmed-meshheading:11438531-Retinal Rod Photoreceptor Cells,
pubmed-meshheading:11438531-Sp1 Transcription Factor,
pubmed-meshheading:11438531-Sp4 Transcription Factor,
pubmed-meshheading:11438531-Transcription, Genetic,
pubmed-meshheading:11438531-Transcription Factors,
pubmed-meshheading:11438531-Transcriptional Activation,
pubmed-meshheading:11438531-Transfection,
pubmed-meshheading:11438531-Xenopus
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pubmed:year |
2001
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pubmed:articleTitle |
Nrl and Sp nuclear proteins mediate transcription of rod-specific cGMP-phosphodiesterase beta-subunit gene: involvement of multiple response elements.
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pubmed:affiliation |
Jules Stein Eye Institute and the Department of Ophthalmology, School of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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