E2A-PBX1 interacts directly with the KIX domain of CBP/p300 in the induction of proliferation in primary hematopoietic cells
E2A-PBX1 interacts directly with the KIX domain of CBP/p300 in the induction of proliferation in primary hematopoietic cells
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DOI：
10.1074/jbc.m408654200
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发表时间：
2004-12-31
影响因子：
4.8
通讯作者：
LeBrun, DP
中科院分区：
文献类型：
--
作者：
Bayly, R;Chuen, L;LeBrun, DP
E2 A基因编码DNA结合转录因子，称为E12和E47，参与细胞的特化和成熟。E2 A还参与染色体易位，导致在急性白血病病例中称为E2 A-PBX 1的致癌转录因子的表达。在这里描述的工作中，我们阐明了E2 A-PBX 1和转录共激活因子之间的相互作用。我们确认E2 A部分可以与CBP和PCAF相互作用，并将所需的元素映射到E2 A和CBP上。在CBP上，相互作用涉及KIX结构域，这是一个充分表征的结构域，介导与其他几种致癌转录因子的相互作用。在E2 A上，与CBP的相互作用需要位于激活结构域1和2（分别为AD 1和AD 2）内的保守α-螺旋结构域。使用纯化的重组蛋白，我们表明E2 A-CBP相互作用是直接的。尽管先前证明的能力，AD 1和AD 2独立运作，我们的一些研究结果表明这两个域之间的功能协同性。最后，我们发现CBP/p300相互作用的螺旋结构域的E2 A是重要的，在培养的原代骨髓细胞的增殖诱导逆转录病毒转导E2 A-PBX 1。我们的研究结果表明，E2 A-PBX 1肿瘤发生的某些方面涉及与CBP/p300的KIX结构域的直接相互作用。
The E2A gene encodes DNA-binding transcription factors, called E12 and E47, involved in cell specification and maturation. E2A is also involved in a chromosomal translocation that leads to the expression of an oncogenic transcription factor called E2A-PBX1 in cases of acute leukemia. In the work described here, we elucidate the interaction between E2A-PBX1 and transcriptional co-activators. We confirm that the E2A portion can interact with CBP and PCAF and map required elements on E2A and CBP. On CBP, the interaction involves the KIX domain, a well characterized domain that mediates interactions with several other oncogenic transcription factors. On E2A, the interaction with CBP requires conserved alpha-helical domains that reside within activation domains 1 and 2 (AD1 and AD2, respectively). Using purified, recombinant proteins, we show that the E2A-CBP interaction is direct. Notwithstanding the previously demonstrated ability of AD1 and AD2 to function independently, some of our findings suggest functional cooperativity between these two domains. Finally, we show that the CBP/p300-interactive helical domains of E2A are important in the induction of proliferation in cultured primary bone marrow cells retrovirally transduced with E2A-PBX1. Our findings suggest that some aspects of E2A-PBX1 oncogenesis involve a direct interaction with the KIX domain of CBP/p300.