DIPA, which can localize to the centrosome, associates with p78/MCRS1/MSP58 and acts as a repressor of gene transcription

DIPA, which can localize to the centrosome, associates with p78/MCRS1/MSP58 and acts as a repressor of gene transcription
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DOI:
10.1016/j.yexmp.2006.07.008
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发表时间:
2006-12-01
影响因子:
3.6
通讯作者:
Greene, Mark I.
Greene, Mark I.
中科院分区:
医学3区
文献类型:
--
作者:
Du, Xiulian;Wang, Qiang;Greene, Mark I.

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DIPA(δ 相互作用蛋白 A)最初被鉴定为与 δ 型肝炎抗原相关的蛋白质。在这项研究中,我们发现 DIPA 可以与 p78/MCRS/MSP58 相关,p78/MCRS/MSP58 是一种含有 Forkhead 相关结构域的蛋白质,与恶性转化以及基因转录和翻译的调节有关。我们通过免疫共沉淀分析了 DIPA 和 p78 之间的相互作用,并确定了参与相互作用的结构区域。与物理相互作用一致,我们发现 DIPA 主要与 p78 共定位于细胞核。此外,可以在中心体上检测到一小部分 DIPA。此外,我们证明 DIPA 可以作为基因转录的阻遏物,p78 似乎可以增强这种活性。总而言之,我们的结果揭示了一种新型蛋白质复合物,它在基因表达和细胞增殖的调节中发挥作用。我们认为 DIPA 功能障碍可能通过影响 p78 的功能而导致恶性转化。 (c) 2006 Elsevier Inc. 保留所有权利。
DIPA (delta-interacting protein A) was initially identified as a protein that associates with the hepatitis delta antigen. In this study, we found that DIPA can associate with p78/MCRS/MSP58, a Forkhead-associated domain containing protein implicated in malignant transformation as well as in regulation of gene transcription and translation. We analyzed the interaction between DIPA and p78 by co-immunoprecipitation and identified the structural regions involved in the interaction. Consistent with the physical interaction, we found that DIPA is predominant colocalized with p78 to the nucleus. In addition, a fraction of DIPA can be detected on the centrosome. Furthermore, we demonstrate that DIPA can act as a repressor of gene transcription, an activity that appears to be enhanced by p78. Taken together, our results revealed a novel protein complex that plays a role in regulation of gene expression and cell proliferation. We propose that dysfunction of DIPA may contribute to malignant transformation by affecting the functions of p78. (c) 2006 Elsevier Inc. All rights reserved.