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Adenoviral E1B55K oncoprotein sequesters candidate leukemia suppressor sequence-specific single-stranded DNA-binding

H B Fleisig1, N I Orazio, H Liang

  • 1Department of Molecular Genetics, MD Anderson Cancer Center, Houston, TX 77030, USA.

Oncogene
|February 22, 2007
PubMed

Insights

Adenoviral oncoprotein E1B55K binds to sequence-specific single-stranded DNA-binding protein 2 (SSBP2), a potential acute myelogenous leukemia (AML) tumor suppressor. E1B55K sequesters SSBP2 into aggresomes, but does not degrade it.

Area of Science:

  • Molecular Biology
  • Oncology
  • Virology

Background:

  • Sequence-specific single-stranded DNA-binding protein 2 (SSBP2) acts as a tumor suppressor in acute myelogenous leukemia (AML).
  • Adenoviral oncoprotein E1B55K is known to interact with cellular proteins and influence cell transformation.

Purpose of the Study:

  • To investigate the interaction between adenoviral oncoprotein E1B55K and SSBP2.
  • To determine the effect of E1B55K on SSBP2 localization and stability.

Main Methods:

  • Co-immunoprecipitation assays to detect protein binding.
  • Immunofluorescence microscopy to visualize protein localization.
  • Cell culture experiments in HEK 293, IMR90, and HeLa cells.

Main Results:

  • Adenoviral E1B55K directly binds to endogenous SSBP2.
  • E1B55K sequesters SSBP2 into juxtanuclear bodies, identified as aggresomes, dependent on intact microtubules.
  • SSBP2 remains associated with E1B55K in nuclear foci when nuclear export is inhibited.
  • Unlike Mre11 and p53, SSBP2 is not degraded by E1B55K.

Conclusions:

  • Adenoviral E1B55K targets the candidate leukemia suppressor SSBP2.
  • Subversion of SSBP2 function by E1B55K may contribute to viral oncoprotein-mediated cell transformation.

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