Roles of HIPK1 and HIPK2 in AML1-and p300-dependent transcription, hematopoiesis and blood vessel formation
Roles of HIPK1 and HIPK2 in AML1-and p300-dependent transcription, hematopoiesis and blood vessel formation
复制标题
DOI：
10.1038/sj.emboj.7601273
复制
发表时间：
2006-09-06
期刊：
影响因子：
11.4
通讯作者：
Kitabayashi, Issay
中科院分区：
文献类型：
--
作者：
Aikawa, Yukiko;Nguyen, Lan Anh;Kitabayashi, Issay
组蛋白乙酰转移酶 (HAT) p300 和 CREB 结合蛋白 (CBP) 作为多种序列特异性转录因子（包括 AML1）的共激活剂。在此，我们报告同源结构域相互作用蛋白激酶 2 (HIPK2) 与 AML1 和 p300 形成复合物，并使 AML1 和 p300 磷酸化以刺激转录激活以及 HAT 活性。 p300 的磷酸化由磷酸化的 AML1 以及 PU.1、c-MYB、c-JUN 和 c-FOS 触发，并被显性失活 HIPK2 抑制。 Hipk1/2 双缺陷小鼠胚胎中 p300 和 AML1 的磷酸化受损。双缺陷小鼠表现出原始/决定性造血、血管生成、血管生成和神经管闭合方面的缺陷。这些表型部分类似于在 p300 和 CBP 缺陷小鼠中观察到的表型。 HIPK2 还以 AML1 依赖性方式磷酸化另一种共激活剂 MOZ。我们讨论了转录因子调节局部组蛋白乙酰化及其靶基因转录的可能机制。
Histone acetyltransferases (HATs) p300 and CREB-binding protein (CBP) function as co-activators for a variety of sequence-specific transcription factors, including AML1. Here, we report that homeodomain-interacting protein kinase-2 (HIPK2) forms a complex with AML1 and p300, and phosphorylates both AML1 and p300 to stimulate transcription activation as well as HAT activities. Phosphorylation of p300 is triggered by phosphorylated AML1 as well as by PU.1, c-MYB, c-JUN and c-FOS, and is inhibited by dominant-negative HIPK2. Phosphorylation of p300 and AML1 is impaired in Hipk1/2 double-deficient mouse embryos. Double-deficient mice exhibit defects in primitive/definitive hematopoiesis, vasculogenesis, angiogenesis and neural tube closure. These phenotypes are in part similar to those observed in p300- and CBP-deficient mice. HIPK2 also phosphorylates another co-activator, MOZ, in an AML1-dependent manner. We discuss a possible mechanism by which transcription factors could regulate local histone acetylation and transcription of their target genes.