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rdf:type |
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lifeskim:mentions |
umls-concept:C0006142,
umls-concept:C0013081,
umls-concept:C0205314,
umls-concept:C0243125,
umls-concept:C0249197,
umls-concept:C0288472,
umls-concept:C0441712,
umls-concept:C0679622,
umls-concept:C0699900,
umls-concept:C0851285,
umls-concept:C1420626
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pubmed:issue |
6
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pubmed:dateCreated |
2010-3-2
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pubmed:abstractText |
14-3-3 proteins regulate many cellular functions, including proliferation. However, the detailed mechanisms by which they control the cell cycle remain to be fully elucidated. We report that one of the 14-3-3 isoforms, 14-3-3tau, is required for the G(1)/S transition through its role in ubiquitin-independent proteasomal degradation of p21. 14-3-3tau binds to p21, MDM2, and the C8 subunit of the 20S proteasome in G(1) phase and facilitates proteasomal targeting of p21. This function of 14-3-3tau may be deregulated in cancer. The overexpression of 14-3-3tau is frequently found in primary human breast cancer and correlates with lower levels of p21 and shorter patient survival. Tenascin-C, an extracellular matrix protein involved in tumor initiation and progression and a known 14-3-3tau inducer, decreases p21 and abrogates adriamycin-induced G(1)/S arrest. It has been known that p21 is required for a proper tamoxifen response in breast cancer. We show that the overexpression of 14-3-3tau inhibits tamoxifen-induced p21 induction and growth arrest in MCF7 cells. Together, the findings of our studies strongly suggest a novel oncogenic role of 14-3-3tau by downregulating p21 in breast cancer. Therefore, 14-3-3tau may be a potential therapeutic target in breast cancer.
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1098-5549
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
30
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1508-27
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pubmed:dateRevised |
2010-9-2
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pubmed:meshHeading |
pubmed-meshheading:20086099-14-3-3 Proteins,
pubmed-meshheading:20086099-Animals,
pubmed-meshheading:20086099-Breast Neoplasms,
pubmed-meshheading:20086099-Cell Line,
pubmed-meshheading:20086099-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:20086099-Down-Regulation,
pubmed-meshheading:20086099-Female,
pubmed-meshheading:20086099-G1 Phase,
pubmed-meshheading:20086099-Humans,
pubmed-meshheading:20086099-Mice,
pubmed-meshheading:20086099-Proteasome Endopeptidase Complex,
pubmed-meshheading:20086099-Protein Binding,
pubmed-meshheading:20086099-Protein Processing, Post-Translational,
pubmed-meshheading:20086099-Protein Stability,
pubmed-meshheading:20086099-Protein Subunits,
pubmed-meshheading:20086099-Proto-Oncogene Proteins c-mdm2,
pubmed-meshheading:20086099-Signal Transduction,
pubmed-meshheading:20086099-Survival Analysis,
pubmed-meshheading:20086099-Tamoxifen,
pubmed-meshheading:20086099-Tenascin,
pubmed-meshheading:20086099-Ubiquitin
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pubmed:year |
2010
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pubmed:articleTitle |
14-3-3Tau regulates ubiquitin-independent proteasomal degradation of p21, a novel mechanism of p21 downregulation in breast cancer.
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pubmed:affiliation |
Division of Hematology and Oncology, Department of Medicine,1 Medical Statistics Section, University of Alabama at Birmingham, Birmingham, Alabama 35294-2182, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, N.I.H., Extramural
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