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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
18
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pubmed:dateCreated |
1999-10-7
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pubmed:abstractText |
PTEN is a recently identified tumor suppressor inactivated in a variety of cancers such as glioblastoma and endometrial and prostate carcinoma. It contains an amino-terminal phosphatase domain and acts as a phosphatidylinositol 3,4,5-trisphosphate phosphatase antagonizing the activity of the phosphatidylinositol 3-OH kinase. PTEN also contains a carboxyl-terminal domain, and we addressed the role of this region that, analogous to the amino-terminal phosphatase domain, is the target of many mutations identified in tumors. Expression of carboxyl-terminal mutants in PTEN-deficient glioblastoma cells permitted the anchorage-independent growth of the cells that otherwise was suppressed by wild-type PTEN. The stability of these mutants in cells was reduced because of rapid degradation. Although the carboxyl-terminal region contains regulatory PEST sequences and a PDZ-binding motif, these specific elements were dispensable for the tumor-suppressor function. The study of carboxyl-terminal point mutations affecting the stability of PTEN revealed that these were located in strongly predicted beta-strands. Surprisingly, the phosphatase activity of these mutants was affected in correlation with the degree of disruption of these structural elements. We conclude that the carboxyl-terminal region is essential for regulating PTEN stability and enzymatic activity and that mutations in this region are responsible for the reversion of the tumor-suppressor phenotype. We also propose that the molecular conformational changes induced by these mutations constitute the mechanism for PTEN inactivation.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10468583-1584778,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10468583-2175676,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10468583-2876518,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10468583-3293597,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10468583-7516475,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10468583-7772023,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10468583-8356056,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10468583-8910511,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10468583-9043636,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10468583-9072974,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10468583-9090379,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10468583-9140396,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10468583-9187108,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10468583-9256433,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10468583-9288766,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10468583-9307275,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10468583-9331071,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10468583-9331072,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10468583-9354433,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/10468583-9371490,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/10468583-9622068,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10468583-9635567,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10468583-9679243,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10468583-9696041,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/10468583-9765621,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10468583-9778245,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10468583-9799739,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10468583-9811831,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10468583-9891051
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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 |
Aug
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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 |
31
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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 |
10182-7
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:10468583-Amino Acid Sequence,
pubmed-meshheading:10468583-Animals,
pubmed-meshheading:10468583-COS Cells,
pubmed-meshheading:10468583-Female,
pubmed-meshheading:10468583-Genes, Tumor Suppressor,
pubmed-meshheading:10468583-Glioblastoma,
pubmed-meshheading:10468583-Humans,
pubmed-meshheading:10468583-Molecular Sequence Data,
pubmed-meshheading:10468583-Mutagenesis, Site-Directed,
pubmed-meshheading:10468583-PTEN Phosphohydrolase,
pubmed-meshheading:10468583-Phosphoric Monoester Hydrolases,
pubmed-meshheading:10468583-Placenta,
pubmed-meshheading:10468583-Point Mutation,
pubmed-meshheading:10468583-Protein Structure, Secondary,
pubmed-meshheading:10468583-Recombinant Proteins,
pubmed-meshheading:10468583-Transfection,
pubmed-meshheading:10468583-Tumor Cells, Cultured,
pubmed-meshheading:10468583-Tumor Suppressor Proteins
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pubmed:year |
1999
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pubmed:articleTitle |
The tumor-suppressor activity of PTEN is regulated by its carboxyl-terminal region.
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pubmed:affiliation |
Laboratory of Molecular Oncology, The Rockefeller University, New York, NY 10021, USA. georgem@rockvax.rockefeller.edu
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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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