Figure 4.

Upstream modulators of epidermal growth factor receptor (EGFR) signaling. Modulators of EGFR include extracellular modulators like semaphorin 3C (SEMA3C) and the androgen derivative 3α-diol, and intracellular modulators like prostaglandin E receptor 3 (EP3), scinderin (SCIN), and ubiquitin-specific peptidase 39 (USP39). Two inhibitors—the CKLF-like MARVEL transmembrane domain-containing 5 (CMTM5) and the phosphatase of regenerating liver 1 (PRL-1)—are identified. In particular, USP39 promotes EGFR signaling by promoting EGFR mRNA maturation. A black arrow represents signal transduction; a black dashed arrow represents translocated small molecules.