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Adenoviral E1B55K oncoprotein sequesters candidate leukemia suppressor sequence-specific single-stranded DNA-binding protein 2 into aggresomes

Oncogene volume 26, pages 4797–4805 (2007)Cite this article

Abstract

Sequence-specific single-stranded DNA-binding protein 2 (SSBP2) is a candidate tumor suppressor for human acute myelogenous leukemia (AML). Inducible expression of SSBP2 causes growth arrest and partial differentiation in AML cells. Here, we report that the adenoviral oncoprotein E1B55K directly binds to endogenous SSBP2 protein and sequesters it into juxtanuclear bodies in adenovirally transformed human embryonic kidney (HEK) 293 cells. Similarly, transient expression of E1B55K in IMR90 fibroblasts and HeLa cells result in the formation of juxtanuclear bodies containing SSBP2. When nuclear export of E1B55K is prevented, SSBP2 remains associated with E1B55K in nuclear foci. A requirement for intact microtubules to retain the integrity of the juxtanuclear bodies suggests them to be E1B55K containing aggresomes. The adenoviral E1B55K protein has been shown to localize to the Mre11 complex and p53 to aggresome structures; together with the viral E4orf6 protein, E1B55K recruits a cellular E3 ubiquitin ligase that induces degradation of Mre11 and p53. However, our present studies reveal that E1B55K does not degrade SSBP2. These data demonstrate that E1B55K targets the candidate leukemia suppressor SSBP2 and suggest that subverting its function may contribute to cell transformation by viral oncoproteins.

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Acknowledgements

We thank V Malhotra, members of the Nagarajan and Weitzman labs for helpful discussions during the course of this work and for critical reading of the manuscript. We thank V Lundblad and her lab for help with two-hybrid experiments and R Schwartz for help with degradation experiment. Work in the Nagarajan laboratory was supported by NIH Grant HL074449. The automated DNA sequencing core facility at MD Anderson cancer center supported by core grant CA16672 is acknowledged for verification of expression of constructs. MDW acknowledges the James B Pendleton Charitable Trust for providing the microscopy suite. Work in the lab of MDW was supported in part by NIH Grant CA97093. NIO was supported by an NIH Training Grant (T32 CA064041) and a fellowship from the Chapman Charitable Trust.

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Author notes

  1. H B Fleisig and N I Orazio: These two authors have contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular Genetics, MD Anderson Cancer Center, Houston, TX, USA

    H B Fleisig, H Liang, A F Tyler, H P Adams & L Nagarajan

  2. Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA

    N I Orazio & M D Weitzman

  3. Division of Biology, Graduate Program, University of California at San Diego, San Diego, CA, USA

    N I Orazio & M D Weitzman

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  1. H B Fleisig
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Correspondence to L Nagarajan.

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Fleisig, H., Orazio, N., Liang, H. et al. Adenoviral E1B55K oncoprotein sequesters candidate leukemia suppressor sequence-specific single-stranded DNA-binding protein 2 into aggresomes. Oncogene 26, 4797–4805 (2007). https://doi.org/10.1038/sj.onc.1210281

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