Thus, this hexapeptide motif is required to confer to Hoxa1 its oncogenic potential, supporting the view that this critically buy ICG-001 relies on the ability of Hoxa1 to interact with Pbx. The involvement of Hox-Pbx interaction in cancer stimulation is supported by several studies aiming at evaluating the impact of HOX-PBX dimer disrupting molecules on cancer cell properties. These molecules were either synthetic peptides mimicking the hexapeptide motif from HOX proteins , or mimetic compounds obtained from molecular modelling and combinatorial libraries . Such antagonist molecules have been shown to specifically block proliferation and promote apoptosis of melanoma, ovarian, pancreatic and non-small-cell lung cancer cells in which members of the HOX family are deregulated . Blocking the activity of HOX protein by interfering with their binding to PBX co-factor also reduced the growth of tumor cells in vivo . The cell behavior modifications induced by these inhibitors of the HOX-PBX interaction were further correlated to transcriptional changes indicative of a loss of malignancy . In a similar approach, Fernandez et al. showed that a dominant negative mutant of PBX reduced the oncogenic activity of HoxB7 and correlated well with increased apoptosis and decreased cell cycling. Finally, mutating the hexapeptide of HOXB4 has also shown to impair its ability to provoke cell transformation . All these studies together with our data suggest that the interaction between Hox and Pbx proteins is a potential therapeutic target for distinct types of cancers. Nevertheless, disrupting the Hox-Pbx interaction could not always result in a simple functional invalidation of the Hox activity. Indeed, a double mutation in the hexapeptide motif of the mouse Hoxb8 did not result in a loss-of-function of the protein as it is shown here for Hoxa1 and as we previously showed for the Hoxa1WM-AA knockin mice . The knockin allele of Hoxb8 coding for a hexapeptide mutant protein indeed appeared as a neomorph.