腺病毒癌蛋白E1B55K介导应激反应中SSBP2和PML的共定位。

Q2 Biochemistry, Genetics and Molecular Biology Journal of Molecular Signaling Pub Date : 2010-06-11 DOI:10.1186/1750-2187-5-6
Helen B Fleisig, Hong Liang, Lalitha Nagarajan
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引用次数: 5

摘要

腺病毒癌蛋白E1B55K在正常细胞中的瞬时表达诱导了聚集体的形成和聚集体中关键宿主蛋白的隔离。我们之前的研究报道了一种候选肿瘤抑制因子序列特异性结合蛋白2 (SSBP2)被募集到腺病毒转化的人胚胎肾293 (HEK293)细胞的聚集体中。为了了解这些细胞中E1B55K-SSBP2相互作用的程度和意义,我们在HEK293细胞中检测了应激条件下SSBP2的定位。仅在HEK293细胞中,SSBP2在核输出抑制、依托泊苷、羟基脲或γ辐射处理下定位于PML-核小体(PML- nbs)。此外,在HEK293细胞中,PML-NBs的大小和数量在24小时内对辐射的响应中增加,类似于先前在其他细胞类型中的发现。尽管如此,我们得出结论,E1B55K破坏了HEK293细胞中SSBP2的功能。这些发现证明了利用HEK293细胞研究DNA损伤反应和其他细胞过程的局限性,因为SSBP2和类似的调节蛋白由于组成性E1B55K的表达而异常定位。
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Adenoviral oncoprotein E1B55K mediates colocalization of SSBP2 and PML in response to stress.

Transient expression of adenoviral oncoprotein E1B55K in normal cells induces aggresome formation and sequestration of critical host proteins in aggresomes. Our previous studies reported that Sequence Specific Binding Protein 2 (SSBP2), a candidate tumor suppressor is recruited to aggresomes in adenovirally transformed human embryonal kidney 293 (HEK293) cells. To understand the extent and significance of the E1B55K-SSBP2 interactions in these cells, we have examined SSBP2 localization under conditions of stress in HEK293 cells. SSBP2 localizes to PML- Nuclear Bodies (PML-NBs) in response to inhibition of nuclear export, treatment with etoposide, hydroxyurea or gamma irradiation only in HEK293 cells. Furthermore, the PML-NBs grow in size and number in response to radiation over a 24 hour period in HEK293 cells analogous to previous findings for other cell types. Nonetheless, we conclude that E1B55K subverts SSBP2 function in HEK293 cells. These findings demonstrate the limitations in using HEK293 cells to study DNA damage response and other cellular processes since SSBP2 and similar regulatory proteins are aberrantly localized due to constitutive E1B55K expression.

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来源期刊
Journal of Molecular Signaling
Journal of Molecular Signaling Biochemistry, Genetics and Molecular Biology-Biochemistry
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期刊介绍: Journal of Molecular Signaling is an open access, peer-reviewed online journal that encompasses all aspects of molecular signaling. Molecular signaling is an exponentially growing field that encompasses different molecular aspects of cell signaling underlying normal and pathological conditions. Specifically, the research area of the journal is on the normal or aberrant molecular mechanisms involving receptors, G-proteins, kinases, phosphatases, and transcription factors in regulating cell proliferation, differentiation, apoptosis, and oncogenesis in mammalian cells. This area also covers the genetic and epigenetic changes that modulate the signaling properties of cells and the resultant physiological conditions.
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