Novel homeodomain-interacting protein kinase family member, HIPK4, phosphorylates human p53 at serine 9.
We describe here the cloning and characterization of a novel mouse homeodomain-interacting protein kinase (HIPK)-like gene, Hipk4. Hipk4 is expressed in lung and in white adipose tissue and encodes a 616 amino acid protein that includes a serine/threonine kinase domain. We demonstrate that HIPK4 could phosphorylate human p53 protein at serine 9, both in vitro and in vivo. Among known p53-responsive promoters, activity of the human survivin promoter, which is repressed by p53, was decreased by HIPK4 in p53 functional A549 cells. Human BCL2-associated X protein-promoter activity was not affected. These findings suggest that phosphorylation of p53 at serine 9 is important for p53 mediated transcriptional repression.
Arai
Shigeki
S
Division of Gene Structure and Function, Research Center for Genomic Medicine, Saitama Medical University, Japan.
Matsushita
Akio
A
Du
Kun
K
Yagi
Ken
K
Okazaki
Yasushi
Y
Kurokawa
Riki
R
D000595:Amino Acid Sequence; D000818:Animals; D002384:Catalysis; D002454:Cell Differentiation; D049109:Cell Proliferation; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D012694:Serine / Q000235:genetics / Q000378:metabolism*; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
C494826:BAX protein, human; C107489:BIRC5 protein, human; D018076:DNA, Complementary; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D012694:Serine; C527527:HIPK4 protein, human; D017346:Protein Serine-Threonine Kinases