Repression of the Antiapoptotic Molecule Galectin-3 by Homeodomain-interacting Protein Kinase 2-activated P53 is Required for P53-induced Apoptosis.
From: Department of Experimental Oncology, Regina Elena Cancer Institute, 00158 Rome, Italy.
Molecular and cellular biology
- Publish Date: Jun 2006
- ISSN: 0270-7306
- Volume: 26
- Issue: 12
- Pages: 4746-57
- Medium: Print
- Language: English
- Citation (JAMA): Cecchinelli Barbara, Lavra Luca, Rinaldo Cinzia, et al. Repression of the Antiapoptotic Molecule Galectin-3 by Homeodomain-interacting Protein Kinase 2-activated P53 is Required for P53-induced Apoptosis.. Mol. Cell. Biol. Jun 2006;26:4746-57
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.
Mesh Headings (Keywords): Animals, Apoptosis, Base Sequence, Carrier Proteins, Cell Line, DNA, Complementary, Galectin 3, Galectins, Humans, Mice, Nuclear Proteins, Phosphorylation, Protein-Serine-Threonine Kinases, Recombinant Proteins, Serine, Tumor Suppressor Protein p53
Check for Full Text / PubMed Unique Identifier (PMID): 16738336
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