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rdf:type |
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lifeskim:mentions |
umls-concept:C0033414,
umls-concept:C0243125,
umls-concept:C0596290,
umls-concept:C0598086,
umls-concept:C0598388,
umls-concept:C0699900,
umls-concept:C0851285,
umls-concept:C1415887,
umls-concept:C1419040,
umls-concept:C1420433,
umls-concept:C1421293,
umls-concept:C1424666,
umls-concept:C2700100
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pubmed:issue |
1
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pubmed:dateCreated |
2009-9-11
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pubmed:abstractText |
The UBE3A/E6-AP is known to function both as an E3 ubiquitin ligase of the ubiquitin proteasome system and as a transcriptional coactivator. E6-AP shows brain-specific imprinting and loss of function of maternally inherited E6-AP causes Angelman syndrome. However, how the loss of function of E6-AP causes disease pathogenesis is poorly understood. Here, we show that E6-AP interacts with and promotes proteasome-mediated degradation of cyclin-dependent kinase inhibitor p27. E6-AP also directly ubiquitinates p27 in an in vitro ubiquitination assay. Partial knockdown of E6-AP increases the level of p27 leading to cell cycle arrest. Interestingly, partial knockdown also increases the transcription of p27. Finally, we have demonstrated the increased levels of p27 in E6-AP-maternal-deficient and null mice brain. Our result suggests that E6-AP not only enhances the degradation but also regulates the expression of p27 and its loss of function in Angelman syndrome might cause cell cycle alteration leading to disease pathogenesis.
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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/Cycloheximide,
http://linkedlifedata.com/resource/pubmed/chemical/Proliferating Cell Nuclear Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Synthesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Ube3a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/p27 antigen
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1095-953X
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
36
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
26-34
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pubmed:meshHeading |
pubmed-meshheading:19591933-Animals,
pubmed-meshheading:19591933-Apoptosis,
pubmed-meshheading:19591933-Brain,
pubmed-meshheading:19591933-COS Cells,
pubmed-meshheading:19591933-Cell Cycle,
pubmed-meshheading:19591933-Cell Line, Tumor,
pubmed-meshheading:19591933-Cell Proliferation,
pubmed-meshheading:19591933-Cells, Cultured,
pubmed-meshheading:19591933-Cercopithecus aethiops,
pubmed-meshheading:19591933-Cycloheximide,
pubmed-meshheading:19591933-Gene Expression Regulation,
pubmed-meshheading:19591933-Immunoprecipitation,
pubmed-meshheading:19591933-Mice,
pubmed-meshheading:19591933-Mice, Inbred C57BL,
pubmed-meshheading:19591933-Mice, Transgenic,
pubmed-meshheading:19591933-Neuroblastoma,
pubmed-meshheading:19591933-Neurons,
pubmed-meshheading:19591933-Proliferating Cell Nuclear Antigen,
pubmed-meshheading:19591933-Protein Synthesis Inhibitors,
pubmed-meshheading:19591933-RNA, Messenger,
pubmed-meshheading:19591933-RNA, Small Interfering,
pubmed-meshheading:19591933-Transfection,
pubmed-meshheading:19591933-Ubiquitin-Protein Ligases,
pubmed-meshheading:19591933-Ubiquitination
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pubmed:year |
2009
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pubmed:articleTitle |
UBE3A/E6-AP regulates cell proliferation by promoting proteasomal degradation of p27.
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pubmed:affiliation |
Cellular and Molecular Neuroscience Laboratory, National Brain Research Centre, Manesar, Gurgaon-122 050, India.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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