Sp100 is important for the stimulatory effect of homeodomain-interacting protein kinase-2 on p53-dependent gene expression.
HIPK2 shows overlapping localization with p53 in promyelocytic leukemia (PML) nuclear bodies (PML-NBs) and functionally interacts with p53 to increase gene expression. Here we demonstrate that HIPK2 and the PML-NB resident protein Sp100 synergize for the activation of p53-dependent gene expression. Sp100 and HIPK2 interact and partially colocalize in PML-NBs. The cooperation of HIPK2 and Sp100 for the induction of p21(Waf1) is completely dependent on the presence of p53 and the kinase function of HIPK2. Downregulation of Sp100 levels by expression of siRNA does not interfere with p53-mediated transcription, but obviates the enhancing effect of HIPK2. In summary, these experiments reveal a novel function for Sp100 as a coactivator for HIPK2-mediated p53 activation.
Möller
Andreas
A
German Cancer Research Center, Division of Immunochemistry (G0200), Im Neuenheimer Feld 280, Heidelberg D-69120, Germany.
Sirma
Hüseyin
H
Hofmann
Thomas G
TG
Staege
Hannah
H
Gresko
Ekaterina
E
Lüdi
Katharina Schmid
KS
Klimczak
Elisabeth
E
Dröge
Wulf
W
Will
Hans
H
Schmitz
M Lienhard
ML
D034961:Antigens, Nuclear / Q000032:analysis / Q000502:physiology*; D001324:Autoantigens / Q000032:analysis / Q000502:physiology*; D002352:Carrier Proteins / Q000032:analysis / Q000502:physiology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; 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*
D034961:Antigens, Nuclear; D001324:Autoantigens; D002352:Carrier Proteins; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; C066642:SP100 protein, human; C115114:HIPK2 protein, human; D017346:Protein Serine-Threonine Kinases