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. Author manuscript; available in PMC: 2023 Apr 1.
Published in final edited form as: Cancer Lett. 2022 Jan 14;530:181–189. doi: 10.1016/j.canlet.2022.01.009

Figure 2.

Figure 2.

Schematic of ETS activation by MAPK and loss of tumor suppressors that activate ETS. A) ETS proteins ERG, ETV1, ETV4, and ETV5 can be phosphorylated by MAPK that activates transcriptional activity. B) PEA3 factors ETV1, ETV4, and ETV5 are ubiquitinated by the E3 ligase COP1 and this process is inhibited by MAPK signaling. COP1 is a tumor suppressor lost in prostate cancer that leads to elevated ETV1/4/5. In addition, most ETV1/4/5 fusions lose the N-terminal domain that contain the degron, leading to stabilized proteins. C) CIC is a transcriptional suppressor of PEA3 factors (especially ETV4) and its activity is inhibited by MAPK signaling. CIC, located next to ERF, is deleted in prostate cancer. D) ERF and ETV3 are ETS transcriptional suppressors that bind to ETS binding sites and inhibit transcription. When phosphorylated by MAPK, they are exported from the nucleus, facilitating positive ETS factors to bind and activate transcription. ERF is mutated and deleted in prostate cancer.