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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
15
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pubmed:dateCreated |
1999-8-23
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pubmed:abstractText |
Alterations in normal protein biogenesis and the resulting accumulation of improperly folded proteins in the endoplasmic reticulum (ER) trigger a stress response that up-regulates the expression of ER chaperones, while coordinately repressing overall protein synthesis and causing cell-cycle arrest. Activation of this unfolded protein response (UPR) in mouse NIH 3T3 fibroblasts with the glycosylation inhibitor tunicamycin led to a decline in cyclin D- and E-dependent kinase activities and to G(1) phase arrest. Cyclin D1 protein synthesis was rapidly inhibited by tunicamycin treatment. However, the drug did not significantly affect the mitogen-dependent activities of the extracellular signal-activated protein kinases ERK1 and ERK2 or the level of cyclin D1 mRNA until much later in the response. Therefore, the UPR triggers a signaling pathway that blocks cyclin D1 translation despite continuous mitogenic stimulation. Enforced overexpression of cyclin D1 in tunicamycin-treated cells maintained cyclin D- and E-dependent kinase activities and kept cells in cycle in the face of a fully activated UPR. Translational regulation of cyclin D1 in response to ER stress is a mechanism for checkpoint control that prevents cell-cycle progression until homeostasis is restored.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10411905-10075928,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10411905-1599691,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10411905-1827757,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10411905-649666,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10411905-7495572,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10411905-7649471,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10411905-7758941,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10411905-7877684,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10411905-7935441,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10411905-7954821,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10411905-8114738,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10411905-8183557,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10411905-8246956,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10411905-8259215,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10411905-8339933,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10411905-8476209,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10411905-8754828,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10411905-9000144,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10411905-9106657,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10411905-9136925,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10411905-9308364,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10411905-9384597,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10411905-9448290,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10411905-9561852,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10411905-9637683,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10411905-9653178,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10411905-9695849,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10411905-9755171,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10411905-9766525,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10411905-9823374,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10411905-9930704
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
20
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pubmed:volume |
96
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
8505-10
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:10411905-3T3 Cells,
pubmed-meshheading:10411905-Animals,
pubmed-meshheading:10411905-Cell Cycle,
pubmed-meshheading:10411905-Cyclin A,
pubmed-meshheading:10411905-Cyclin D1,
pubmed-meshheading:10411905-Cyclin-Dependent Kinases,
pubmed-meshheading:10411905-Flow Cytometry,
pubmed-meshheading:10411905-G1 Phase,
pubmed-meshheading:10411905-Gene Expression Regulation,
pubmed-meshheading:10411905-Mice,
pubmed-meshheading:10411905-Protein Biosynthesis,
pubmed-meshheading:10411905-Protein Folding,
pubmed-meshheading:10411905-Protein Synthesis Inhibitors,
pubmed-meshheading:10411905-RNA, Messenger,
pubmed-meshheading:10411905-Signal Transduction,
pubmed-meshheading:10411905-Tunicamycin
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pubmed:year |
1999
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pubmed:articleTitle |
Mammalian unfolded protein response inhibits cyclin D1 translation and cell-cycle progression.
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pubmed:affiliation |
Department of Tumor Cell Biology, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105, 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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