TP53INP1s and homeodomain-interacting protein kinase-2 (HIPK2) are partners in regulating p53 activity.
The TP53INP1 gene encodes two protein isoforms, TP53INP1alpha and TP53INP1beta, located into the nucleus. Their synthesis is increased during cellular stress by p53-mediated activation of transcription. Overexpression of these isoforms induces apoptosis, suggesting an involvement of TP53INP1s in p53-mediated cell death. It was recently shown that p53-dependent apoptosis is promoted by homeodomain-interacting protein kinase-2 (HIPK2), which is known to bind p53 and induce its phosphorylation in promyelocytic leukemia protein nuclear bodies (PML-NBs). In this work we show that TP53INP1s localize with p53, PML-IV, and HIPK2 into the PML-NBs. In addition, we show that TP53INP1s interact physically with HIPK2 and p53. In agreement with these results we demonstrate that TP53INP1s, in association with HIPK2, regulate p53 transcriptional activity on p21, mdm2, pig3, and bax promoters. Furthermore, TP53INP1s overexpression induces G1 arrest and increases p53-mediated apoptosis. Although a TP53INP1s and HIPK2 additive effect was observed on apoptosis, G1 arrest was weaker when HIPK2 was transfected together with TP53INP1. These results indicate that TP53INP1s and HIPK2 could be partners in regulating p53 activity.
Tomasini
Richard
R
Centre de Recherche INSERM, EMI 0116, 163 Avenue de Luminy, BP172, Parc Scientifique et Technologique de Luminy, 13009 Marseille, France.
Samir
Amina Azizi
AA
Carrier
Alice
A
Isnardon
Daniel
D
Cecchinelli
Barbara
B
Soddu
Silvia
S
Malissen
Bernard
B
Dagorn
Jean-Charles
JC
Iovanna
Juan L
JL
Dusetti
Nelson J
NJ
D017209:Apoptosis; D002352:Carrier Proteins / Q000032:analysis / Q000502:physiology*; D002453:Cell Cycle; D002478:Cells, Cultured; D006360:Heat-Shock Proteins; D006801:Humans; D009687:Nuclear Proteins / Q000032:analysis / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000502:physiology*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D002352:Carrier Proteins; D006360:Heat-Shock Proteins; D009687:Nuclear Proteins; C429767:TP53INP1 protein, human; D016159:Tumor Suppressor Protein p53; C115114:HIPK2 protein, human; D017346:Protein Serine-Threonine Kinases