C. Abramovich et al., Functional cloning and characterization of a novel nonhomeodomain protein that inhibits the binding of PBX1-HOX complexes to DNA, J BIOL CHEM, 275(34), 2000, pp. 26172-26177
PBX1 is a homeodomain protein that functions in complexes with other homeod
omain-containing proteins to regulate gene expression during developmental
and/or differentiation processes. A yeast two hybrid screen of a fetal live
r-hematopoietic cDNA library using PBX1a as bait led to the discovery of a
novel non-homeodomain-containing protein that interacts with PBX1 as well a
s PBX2 and PBX3. RNA analysis revealed it to be expressed in CD34(+) hemato
poietic cell populations enriched in primitive progenitors, as is PBX1; sea
rch of the expressed sequence tag data base indicated that it is also expre
ssed in other early embryonic as well as adult tissues. The full-length cDN
A encodes a 731-amino acid protein that has no significant homology to know
n proteins. This protein that we have termed hematopoietic PBX-interacting
protein (HPIP) is mainly localized in the cytosol and in small amounts in t
he nucleus. The region of PBX that interacts with HPIP includes both the ho
meodomain and immediate N-terminal flanking sequences. Strikingly, electrop
horetic mobility shift assays revealed that HPIP inhibits the ability of PB
X-HOX heterodimers to bind to target sequences. Moreover, HPIP strongly inh
ibits the transactivation activity of ESA-PBX. Together these findings sugg
est that HPIP is a new regulator of PBX function.