title: HIPK1 interacts with c-Myb and modulates its activity through phosphorylation.
abstract: The transcription factor v-Myb is a potent inducer of myeloid leukaemias, and its cellular homologue c-Myb plays a crucial role in the regulation of haematopoiesis. In a yeast two-hybrid (Y2H) screening we identified the nuclear kinase HIPK1 as an interaction partner for human c-Myb. The interaction involves a C-terminal region of HIPK1, while a bipartite interaction surface was identified in c-Myb, including regions in its N-terminal DNA-binding domain as well as in its C-terminal region. HIPK1 and c-Myb co-localize in distinct nuclear foci upon co-transfection. c-Myb appears to be phosphorylated by HIPK1 in its negative regulatory domain as supported by both in vivo and in vitro data. A functional assay revealed that HIPK1 repressed the ability of c-Myb to activate a chromatin embedded target gene, mim-1, in haematopoetic cells. Our findings point to a novel link between an important kinase and a key regulator of haematopoiesis.
authors: Department of Molecular Biosciences, University of Oslo, Norway.
authors: Vilborg
authors: V
authors: Matre
authors: Oddmund
authors: O
authors: Nordgård
authors: Anne Hege
authors: AH
authors: Alm-Kristiansen
authors: Marit
authors: M
authors: Ledsaak
authors: Odd Stokke
authors: OS
authors: Gabrielsen
mesh_terms: D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D020798:Two-Hybrid System Techniques
chemical_list: D020598:Proto-Oncogene Proteins c-myb; C543644:HIPK1 protein, human; D017346:Protein Serine-Threonine Kinases