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Blood, 1 July 2001, Vol. 98, No. 1, pp. 201-209
NEOPLASIA
EAF1, a novel ELL-associated factor
that is delocalized by expression of the MLL-ELL
fusion protein
Federico Simone,
Paul E. Polak,
Joseph J. Kaberlein,
Roger T. Luo,
Denise A. Levitan, and
Michael
J. Thirman
From the Section of Hematology/Oncology, University of
Chicago, Chicago, IL.
The (11;19)(q23;p13.1) translocation in acute leukemia leads to the
generation of a chimeric protein that fuses MLL to the transcriptional
elongation factor ELL. A novel protein was isolated from a yeast
2-hybrid screen with ELL that was named EAF1 for ELL-associated factor
1. Using specific antibodies, the endogenous EAF1 and ELL proteins were
coimmunoprecipitated from multiple cell lines. In addition, endogenous
EAF1 also exhibited the capacity to interact with ELL2. Database
comparisons with EAF1 identified a region with a high content of
serine, aspartic acid, and glutamic acid residues that exhibited
homology with the transcriptional activation domains of several
translocation partner proteins of MLL, including AF4, LAF4, and AF5q31.
A similar transcriptional activation domain has been identified in this
region of EAF1. By confocal microscopy, endogenous EAF1 and ELL
colocalized in a distinct nuclear speckled pattern. Transfection of the
MLL-ELL fusion gene delocalized EAF1 from its nuclear
speckled distribution to a diffuse nucleoplasmic pattern. In leukemic
cell lines derived from mice transplanted with
MLL-ELL-transduced bone marrow, EAF1 speckles were not
detected. Taken together, these data suggest that expression of the
MLL-ELL fusion protein may have a dominant effect on the normal
protein-protein interactions of ELL.

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