Figure 3 |. LHPP is a protein histidine phosphatase and a tumour suppressor.

a, b, Immunoblot analysis (a) and quantification (b), shows increased 3-pHis and 1-pHis signals in L-dKO tumours (20 weeks) compared to control (ctrl) littermates. Similar results were observed in tumours from L-dKO mice (n = 4). Tissue lysates in 2× sample buffer (pH 8.8) heated at 95 °C for 10 min were dephosphorylated and served as a control. For full scans, see Supplementary Fig. 5. In the 3-pHis blot, the area enclosed in the dashed line was used for quantification (n = 4). Adjusted *P = 0.0460, **P = 0.0051, two-sided, Holm-Sidak’smultiple comparisons test. Data are mean ± s.d. M, molecular mass. c, Immunoblotting shows a reduction in 3-pHis levels in CB1 cells infected with adenovirus (adeno) containing LHPP, compared to cells infected with a control adenovirus. Similar results were observed in three biological experiments. For full scans, see Supplementary Fig. 7. d, Quantification of immunoblots indicate that 3-pHis signals are significantly reduced upon LHPP re-expression compared to control-infected cells (n = 3 biological repeats). ****P < 0.0001, two-sided ratio paired t-test. NS, not significant. Data are mean ± s.d. e, Top, experimental timeline. AAV-control or AAV-LHPP was injected into the tail vein of 8-week-old L-dKO and littermate control mice. Bottom, representative images of whole livers showing reduction in L-dKO liver tumour burden after infection with AAV-LHPP compared to infection with AAV-control (arrowheads indicate tumours). Similar results were observed in five different L-dKO mice infected with AAV-LHPP. f, Photographs of tumours isolated from L-dKO mice infected with AAV-LHPP and AAV-control. g, Quantification of tumours in L-dKO mice showing a significant reduction in tumour burden after infection with AAV-LHPP (n = 5 mice), compared to AAV-control (n = 6 mice). ****P < 0.0001, two-sided unpaired t-test. Data are mean ± s.d.