1: Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):470-4. 

Selective repression of transcriptional activators by Pbx1 does not require the
homeodomain.

Lu Q, Kamps MP.

Department of Pathology, University of California, San Diego, School of
Medicine, La Jolla 92093, USA.

PBX1 is a homeobox-containing gene identified as the chromosome 1 participant of
the t(1;19) chromosomal translocation of childhood pre-B-cell acute
lymphoblastic leukemia. This translocation produces a fusion gene encoding the
chimeric oncoprotein E2A-Pbx1, which can induce both acute myeloid and
T-lymphoid leukemia in mice. The binding of Pbx1 to DNA is weak; however, both
Pbx1 and E2A-Pbx1 exhibit tight binding to specific DNA motifs in conjunction
with certain other homeodomain proteins, and E2A-Pbx1 activates transcription
through these motifs, whereas Pbx1 does not. In this report, we investigate
potential transcriptional functions of Pbx1, using transient expression assays.
While no segments of Pbx1 activated transcription, an internal domain of Pbx1
repressed transcription induced by the activation domain of Sp1, but not by the
activation domains of VP16 or p53. This Pbx1 domain, which lies upstream of the
homeodomain and is highly conserved among Pbx proteins, is thus predicted to
bind a specific transcription factor. Surprisingly, the repression activity of
Pbx1 did not require homeodomain-dependent DNA binding. Thus, Pbx1 may be able
to alter gene transcription by both DNA-binding-dependent and
DNA-binding-independent mechanisms.

PMID: 8552663 [PubMed - indexed for MEDLINE]


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