Matre Vilborg, Nordgård Oddmund, Alm-Kristiansen Anne Hege, Ledsaak Marit, Gabrielsen Odd Stokke
Department of Molecular Biosciences, University of Oslo, Norway.
Biochem Biophys Res Commun. 2009 Oct 9;388(1):150-4. doi: 10.1016/j.bbrc.2009.07.139. Epub 2009 Jul 30.
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.
转录因子v-Myb是髓系白血病的强效诱导剂，其细胞同源物c-Myb在造血调控中起关键作用。在酵母双杂交（Y2H）筛选中，我们鉴定出核激酶HIPK1是人c-Myb的相互作用伴侣。这种相互作用涉及HIPK1的C末端区域，而在c-Myb中鉴定出一个二分相互作用表面，包括其N末端DNA结合结构域以及C末端区域中的区域。共转染后，HIPK1和c-Myb在不同的核灶中共定位。体内和体外数据均支持c-Myb在其负调控结构域中似乎被HIPK1磷酸化。功能分析表明，HIPK1抑制了c-Myb在造血细胞中激活染色质嵌入靶基因mim-1的能力。我们的发现指出了一种重要激酶与造血关键调节因子之间的新联系。
