Lee Wendy, Andrews Bryan C, Faust Michael, Walldorf Uwe, Verheyen Esther M
Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada.
Dev Biol. 2009 Jan 1;325(1):263-72. doi: 10.1016/j.ydbio.2008.10.029. Epub 2008 Nov 5.
Homeodomain interacting protein kinase (Hipk) is a member of a novel family of serine/threonine kinases. Extensive biochemical studies of vertebrate homologs, particularly Hipk2, have identified a growing list of interactors, including proteins involved in transcriptional regulation, chromatin remodeling and essential signaling pathways such as Wnt and TGFbeta. To gain insight into the in vivo functions of the single Drosophila Hipk we characterized loss of function alleles, which revealed an essential requirement for hipk. We find that in the developing eye, hipk promotes the Notch pathway. Notch signaling acts at multiple points in eye development to promote growth, proliferation and patterning. Hipk stimulates the early function of Notch in promotion of global growth of the eye disc. It has been shown in the Drosophila eye that Hipk interferes with the repressive activity of the global co-repressor, Groucho (Gro). Here, we propose that Hipk antagonizes Gro to promote the transmission of the Notch signal, indicating that Hipk plays numerous roles in regulating gene expression through interference with the formation of Gro-containing co-repressor complexes.
同源结构域相互作用蛋白激酶（Hipk）是丝氨酸/苏氨酸激酶新家族的成员。对脊椎动物同源物，特别是Hipk2进行的广泛生化研究，已经确定了越来越多的相互作用蛋白，包括参与转录调控、染色质重塑以及Wnt和TGFβ等重要信号通路的蛋白质。为了深入了解果蝇中单一Hipk的体内功能，我们对功能缺失等位基因进行了表征，结果揭示了对hipk的基本需求。我们发现，在发育中的眼睛中，hipk促进Notch信号通路。Notch信号在眼睛发育的多个阶段发挥作用，以促进生长、增殖和模式形成。Hipk刺激Notch在促进眼盘整体生长方面的早期功能。在果蝇眼睛中已经表明，Hipk会干扰全局共抑制因子Groucho（Gro）的抑制活性。在这里，我们提出Hipk拮抗Gro以促进Notch信号的传递，这表明Hipk通过干扰含Gro的共抑制因子复合物的形成，在调节基因表达中发挥多种作用。
