Fig. 4: PI3K/AKT regulates TRIM21 and PPP in vivo and in human cancers.

a–d Pten null prostate cancer and T-ALL mouse models have higher levels of G6PD protein and PPP metabolites as well as lower levels of Trim21, which could be reverted by PKI-587 treatment. The cell lysates from the anterior lobes of the prostates of Pb-Cre⁻;Pten^L/L and Pb-Cre⁺;Pten^L/L models (a) and the thymic cells of VEC⁻Cre⁻;Pten^L/L and VEC⁻Cre⁺;Pten^L/L mice (b) without and with PKI-587 (25 mg/kg) treatment; the Trim21 mRNA levels (c) and PPP metabolites were measured (d) 24 h later. Median and quartile values are provided by the central line and box boundaries. Whiskers show min to max values. e PTEN WT/CS-inducible PC3 cells were treated with Dox (2 μg/ml) for the indicated time periods. The TRIM21 mRNA and protein levels were measured by RT-qPCR, and cell lysates were subjected to immunoblotting with the indicated antibodies. f PC3 cells were treated with PKI-587 (1 µM) for the indicated time periods. The TRIM21 mRNA levels were measured by RT-qPCR, and cell lysates were subjected to immunoblotting with the indicated antibodies. g Human T-ALL and LNCAP prostate cancer cells were treated with PKI-587 (1 µM) for the indicated time periods. The TRIM21 mRNA and protein levels were measured by RT-qPCR, and cell lysates were subjected to immunoblotting with the indicated antibodies. h Correlations between the PI3K pathway activity score and the TRIM21 mRNA levels in human thyroid and testicular cancers. Data are presented as fold changes and the mean ± SD and were compared with WT or untreated cells. Each experiment was performed n = 3 (c) and n = 4 (e–g) independent times. *p < 0.05, **p < 0.001, and ***p < 0.001, based on Student’s t test (two-sided ANOVA). See also Supplementary Fig. 4. Source data are provided as a Source Data file.