| Cdk5 suppresses the neuronal cell cycle by disrupting the E2F1-DP1 complex. | |
| | |
MedLine Citation:
|
PMID: 20392944 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Neurons that reenter a cell cycle after maturation are at increased risk for death, yet the mechanisms by which a normal neuron suppresses the cycle remain mostly unknown. Our laboratory has shown that cyclin-dependent kinase 5 (Cdk5) is a potent cell cycle suppressor, and we report here on the molecular basis of this activity. Cell cycle suppression by Cdk5 requires its binding to the p35 activator protein. The related p39 and p25 proteins cannot serve as substitutes. Unexpectedly, Cdk5 enzymatic activity is not required to perform this function. Rather, the link to cell cycle regulation is made through the formation of a previously unknown complex consisting of the p35-Cdk5 dimer and E2F1. Formation of this complex excludes the E2F1 cofactor, DP1, thus inhibiting E2F1 binding to the promoters of various cell cycle genes. This anti-cell cycle activity is most likely a neuroprotective function of Cdk5. |
| | |
Authors:
|
Jie Zhang; Huifang Li; Odessa Yabut; Haley Fitzpatrick; Gabriella D'Arcangelo; Karl Herrup |
Related Documents
:
|
7804324 - The steady state levels and structure of the u7 snrnp are constant during the human cel... 18466334 - Cell cycle-driven neuronal apoptosis specifically linked to amyloid peptide abeta1-42 e... 21240854 - Biochemical and pathological studies on the effects of levamisole and chlorambucil on e... 1596534 - Clonal heterogeneity in specific growth rate of saccharomyces cerevisiae cells. 15564714 - Production of endothelin-1 and big endothelin-1 by human cardiac myxoma cells--implicat... 11087054 - Transthyretin and transferrin in hemangioblastoma stromal cells. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
|
Title: The Journal of neuroscience : the official journal of the Society for Neuroscience Volume: 30 ISSN: 1529-2401 ISO Abbreviation: J. Neurosci. Publication Date: 2010 Apr |
Date Detail:
|
Created Date: 2010-04-15 Completed Date: 2010-05-14 Revised Date: 2012-06-25 |
Medline Journal Info:
|
Nlm Unique ID: 8102140 Medline TA: J Neurosci Country: United States |
Other Details:
|
Languages: eng Pagination: 5219-28 Citation Subset: IM |
Affiliation:
|
Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Brain / enzymology, physiology Cell Cycle / physiology* Cell Line, Tumor Cell Nucleus / physiology Cells, Cultured Cyclin-Dependent Kinase 5 / deficiency, genetics, metabolism* Cytoplasm / physiology DNA / metabolism E2F1 Transcription Factor / metabolism* Mice Mice, Inbred C57BL Mice, Transgenic Models, Neurological Nerve Tissue Proteins / metabolism Neurons / enzymology, physiology* Phosphotransferases / metabolism* Transcription Factor DP1 / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
|
NS20591/NS/NINDS NIH HHS; R01 NS020591-26A2/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Cdk5r protein, mouse; 0/E2F1 Transcription Factor; 0/E2f1 protein, mouse; 0/Nerve Tissue Proteins; 0/Tfdp1 protein, mouse; 0/Transcription Factor DP1; 0/p25 protein, mouse; 9007-49-2/DNA; EC 2.7.-/Phosphotransferases; EC 2.7.11.22/Cdk5 protein, mouse; EC 2.7.11.22/Cyclin-Dependent Kinase 5 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Neural precursor death is central to the pathogenesis of intestinal aganglionosis in Ret hypomorphic...
Next Document: During visual word recognition, phonology is accessed within 100 ms and may be mediated by a speech ...