Repression of the antiapoptotic molecule galectin-3 by homeodomain- interacting protein kinase 2-activated p53 is required for p53-induced apoptosis

Barbara Cecchinelli, Luca Lavra, Cinzia Rinaldo, Stefano Iacovelli, Aymone Gurtner, Alessandra Gasbarri, Alessandra Ulivieri, Fabrizio Del Prete, Maria Trovato, Giulia Piaggio, Armando Bartolazzi, Silvia Soddu, Salvatore Sciacchitano

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Galectin 3 (Gal-3), a member of the β-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 HIPK1 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 HIPK1-activated p53 and requiring repression of the antiapoptotic factor Gal-3.

Original languageEnglish
Pages (from-to)4746-4757
Number of pages12
JournalMolecular and Cellular Biology
Volume26
Issue number12
DOIs
Publication statusPublished - Jun 2006

Fingerprint

Galectin 3
Homeodomain Proteins
Protein Kinases
Apoptosis
Galactosides
RNA Interference
Lectins
Genes
Phosphotransferases
Phosphorylation
Neoplasms

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Repression of the antiapoptotic molecule galectin-3 by homeodomain- interacting protein kinase 2-activated p53 is required for p53-induced apoptosis. / Cecchinelli, Barbara; Lavra, Luca; Rinaldo, Cinzia; Iacovelli, Stefano; Gurtner, Aymone; Gasbarri, Alessandra; Ulivieri, Alessandra; Del Prete, Fabrizio; Trovato, Maria; Piaggio, Giulia; Bartolazzi, Armando; Soddu, Silvia; Sciacchitano, Salvatore.

In: Molecular and Cellular Biology, Vol. 26, No. 12, 06.2006, p. 4746-4757.

Research output: Contribution to journalArticle

Cecchinelli, B, Lavra, L, Rinaldo, C, Iacovelli, S, Gurtner, A, Gasbarri, A, Ulivieri, A, Del Prete, F, Trovato, M, Piaggio, G, Bartolazzi, A, Soddu, S & Sciacchitano, S 2006, 'Repression of the antiapoptotic molecule galectin-3 by homeodomain- interacting protein kinase 2-activated p53 is required for p53-induced apoptosis', Molecular and Cellular Biology, vol. 26, no. 12, pp. 4746-4757. https://doi.org/10.1128/MCB.00959-05
Cecchinelli, Barbara ; Lavra, Luca ; Rinaldo, Cinzia ; Iacovelli, Stefano ; Gurtner, Aymone ; Gasbarri, Alessandra ; Ulivieri, Alessandra ; Del Prete, Fabrizio ; Trovato, Maria ; Piaggio, Giulia ; Bartolazzi, Armando ; Soddu, Silvia ; Sciacchitano, Salvatore. / Repression of the antiapoptotic molecule galectin-3 by homeodomain- interacting protein kinase 2-activated p53 is required for p53-induced apoptosis. In: Molecular and Cellular Biology. 2006 ; Vol. 26, No. 12. pp. 4746-4757.
@article{53a7c960eb0a4504b9715e98fcac0398,
title = "Repression of the antiapoptotic molecule galectin-3 by homeodomain- interacting protein kinase 2-activated p53 is required for p53-induced apoptosis",
abstract = "Galectin 3 (Gal-3), a member of the β-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 HIPK1 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 HIPK1-activated p53 and requiring repression of the antiapoptotic factor Gal-3.",
author = "Barbara Cecchinelli and Luca Lavra and Cinzia Rinaldo and Stefano Iacovelli and Aymone Gurtner and Alessandra Gasbarri and Alessandra Ulivieri and {Del Prete}, Fabrizio and Maria Trovato and Giulia Piaggio and Armando Bartolazzi and Silvia Soddu and Salvatore Sciacchitano",
year = "2006",
month = "6",
doi = "10.1128/MCB.00959-05",
language = "English",
volume = "26",
pages = "4746--4757",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "12",

}

TY - JOUR

T1 - Repression of the antiapoptotic molecule galectin-3 by homeodomain- interacting protein kinase 2-activated p53 is required for p53-induced apoptosis

AU - Cecchinelli, Barbara

AU - Lavra, Luca

AU - Rinaldo, Cinzia

AU - Iacovelli, Stefano

AU - Gurtner, Aymone

AU - Gasbarri, Alessandra

AU - Ulivieri, Alessandra

AU - Del Prete, Fabrizio

AU - Trovato, Maria

AU - Piaggio, Giulia

AU - Bartolazzi, Armando

AU - Soddu, Silvia

AU - Sciacchitano, Salvatore

PY - 2006/6

Y1 - 2006/6

N2 - Galectin 3 (Gal-3), a member of the β-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 HIPK1 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 HIPK1-activated p53 and requiring repression of the antiapoptotic factor Gal-3.

AB - Galectin 3 (Gal-3), a member of the β-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 HIPK1 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 HIPK1-activated p53 and requiring repression of the antiapoptotic factor Gal-3.

UR - http://www.scopus.com/inward/record.url?scp=33745020886&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745020886&partnerID=8YFLogxK

U2 - 10.1128/MCB.00959-05

DO - 10.1128/MCB.00959-05

M3 - Article

VL - 26

SP - 4746

EP - 4757

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 12

ER -