| Activation of p38- and CRM1-dependent nuclear export promotes E2F1 degradation during keratinocyte differentiation. | |
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MedLine Citation:
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PMID: 16924238 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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E2F factors modulate a plethora of cell functions, including proliferation, differentiation, DNA repair and apoptosis. We have shown that differentiation in primary epidermal keratinocytes leads to E2F1 downregulation via activation of protein kinase C and p38 mitogen-activated protein kinase. We now demonstrate that E2F1 downregulation in differentiating keratinocytes involves its ubiquitination, as well as proteasomal degradation subsequent to CRM1-dependent nuclear export. E2F1 nuclear export specifically in response to differentiation requires regions adjacent to the cyclin A-binding domain in the N-terminus of this protein. Significantly, inhibition of p38 interferes with nuclear export and degradation of E2F1 during differentiation, but has no effect on E2F1 in undifferentiated cells. Thus, induction of differentiation in epidermal keratinocytes activates a specific program for post-transcriptional downregulation of E2F1, which involves signaling through p38 and activation of nuclear export pathways. |
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Authors:
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I A Ivanova; L Dagnino |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-08-21 |
Journal Detail:
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Title: Oncogene Volume: 26 ISSN: 0950-9232 ISO Abbreviation: Oncogene Publication Date: 2007 Feb |
Date Detail:
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Created Date: 2007-02-22 Completed Date: 2007-03-22 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 8711562 Medline TA: Oncogene Country: England |
Other Details:
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Languages: eng Pagination: 1147-54 Citation Subset: IM |
Affiliation:
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Department of Physiology and Pharmacology and Regulatory Biology, University of Western Ontario, London, Ontario, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Active Transport, Cell Nucleus Animals Cell Differentiation / genetics* Cell Nucleus / chemistry, metabolism* Cells, Cultured Cytoplasm / chemistry, metabolism Down-Regulation E2F1 Transcription Factor / analysis, genetics, metabolism* Enzyme Activation Karyopherins / metabolism* Keratinocytes / chemistry, cytology*, metabolism Mice Mutation Proteasome Endopeptidase Complex / metabolism Protein Structure, Tertiary Receptors, Cytoplasmic and Nuclear / metabolism* Signal Transduction Ubiquitin / metabolism p38 Mitogen-Activated Protein Kinases / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/E2F1 Transcription Factor; 0/Karyopherins; 0/Receptors, Cytoplasmic and Nuclear; 0/Ubiquitin; 0/exportin 1 protein; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 3.4.25.1/Proteasome Endopeptidase Complex |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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