Abstract
Galectin 3 (Gal-3), a member of the beta-galactoside binding lectin family, exhibits antiapoptotic functions, and its aberrant expression is involved in various aspects of tumor progression. Here we show that p53-induced apoptosis is associated with transcriptional repression of Gal-3. Previously, it has been reported that phosphorylation of p53 at Ser46 is important for transcription of proapoptotic genes and induction of apoptosis and that homeodomain-interacting protein kinase 2 (HIPK2) is specifically involved in these functions. We show that HIPK2 cooperates with p53 in Gal-3 repression and that this cooperation requires HIPK2 kinase activity. Gene-specific RNA interference demonstrates that HIPK2 is essential for repression of Gal-3 upon induction of p53-dependent apoptosis. Furthermore, expression of a nonrepressible Gal-3 prevents HIPK2- and p53-induced apoptosis. These results reveal a new apoptotic pathway induced by HIPK2-activated p53 and requiring repression of the antiapoptotic factor Gal-3.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / physiology*
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Base Sequence
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Line
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DNA, Complementary / genetics
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Galectin 3 / antagonists & inhibitors
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Galectin 3 / genetics
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Galectin 3 / metabolism*
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Galectins / antagonists & inhibitors
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Galectins / genetics
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Galectins / metabolism*
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Humans
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Mice
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Nuclear Proteins / antagonists & inhibitors
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Phosphorylation
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Recombinant Proteins / antagonists & inhibitors
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Serine / chemistry
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Tumor Suppressor Protein p53 / chemistry
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism*
Substances
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Carrier Proteins
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DNA, Complementary
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Galectin 3
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Galectins
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Lgals3 protein, mouse
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Nuclear Proteins
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Recombinant Proteins
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TP53 protein, human
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Tumor Suppressor Protein p53
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Serine
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HIPK2 protein, human
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Protein Serine-Threonine Kinases