High risk HPV E6 oncoproteins impair the subcellular distribution of the four and a half LIM-only protein 2 (FHL2).

HPVs are the causative agents of approximately 5% of all human cancers, with cervical cancer being the most predominant. To understand the mechanism of action of the viral E6 oncoprotein, we analysed the effects of E6 upon potential cellular target proteins. One candidate is FHL-2, involved in the regulation of signal transduction pathways from the multimeric complexes assembled at focal adhesions. We show that both HPV E6 and E6(⁎) can interact with FHL-2 in vitro, but unlike most E6 targets, FHL-2 does not appear to be an E6 degradation target. Analysis of the patterns of FHL-2 distribution within HPV-positive tumour-derived cells shows a significant alteration in the pattern of FHL-2 localisation when compared to non-HPV containing cells. This perturbation of FHL-2 distribution is proteasome-dependent and inhibition of E6 expression restores the normal distribution of FHL-2. These results confirm FHL-2 as a new interacting partner of the HPV-E6 oncoproteins.