Supplementary Materials

The PDF file includes:

  • Materials and Methods
  • Fig. S1. Castration of PtenL/L mice decreases AR, AR activity, and 4EBP1 without affecting eIF4F components.
  • Fig. S2. AR regulates 4ebp1 transcription but does not affect translation efficiency or degradation rates.
  • Fig. S3. Androgen deprivation is associated with decreased 4EBP1 expression; DHT add back decreases de novo protein synthesis.
  • Fig. S4. AR binds to an ARE in 4ebp1 in both normal and cancerous prostates, rendering 4EBP1 AR responsive.
  • Fig. S5. Castrate PtenL/L mice develop highly aggressive, nonneuroendocrine tumors independent of PI3K or MNK1/2 activity.
  • Fig. S6. AR/eIF4F-sensitive mRNAs are distinct from mTOR inhibition–sensitive mRNAs.
  • Fig. S7. Protein but not mRNA expression of GRTE-containing proliferation regulators is responsive to changes in eIF4F activity.
  • Fig. S8. Decreased eIF4F complex formation by 4EBP1M results in smaller and less aggressive tumors in castrate PtenL/L;4ebp1M mice.
  • Fig. S9. Castrate PtenL/L mice exhibit increased sensitivity to eIF4F disruption; 4EBP1 abundance is independent of AR in HSPC.
  • Fig. S10. 4E2RCat and 4EGI-1 disrupt eIF4F complex formation in PtenL/L cells, AR+ parental, and AR APIPC cells.
  • Fig. S11. AR- and eIF4F-targeted combinatorial treatments in LNCaP prostate cancer cells demonstrate antitumor activity.
  • Fig. S12. AR shapes the prostate cancer proteome through 4EBP1 and a druggable pro-proliferation translational regulon.
  • Table S1. mRNA expression of AR signature genes comparing castrate PtenL/L ventral prostates to intact PtenL/L ventral prostates.
  • Table S2. Position-weighted map of the 5′UTR GRTE.
  • Table S3. Primers used in this study.
  • References (4547)

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Other Supplementary Material for this manuscript includes the following:

  • Data file S1 (Microsoft Excel format). Translationally up-regulated genes in the castrate PtenL/L mouse.
  • Data file S2 (Microsoft Excel format). Tumor measurements from in vivo experiments.