Zinc finger CCCH domain-containing protein 15 (ZC3H15)

Zinc finger CCCH domain-containing protein 15 (ZC3H15) is a highly conserved eukaryotic protein containing two CCCH-type zinc finger domains and a DFRP (DRG family regulatory protein) domain. By binding RNA and cadherins, ZC3H15 regulates protein metabolism and enhances the GTPase activity of its binding partner DRG1, protecting it from proteolytic degradation. ZC3H15 is implicated in tumorigenesis: it is overexpressed in several human cancers, including gastric cancer, hepatocellular carcinoma, acute myeloid leukemia, and glioblastoma, where its expression correlates with poor patient survival. It promotes cancer cell proliferation, migration, invasion, and tumor growth by modulating key signaling pathways (such as c-Myc and EGFR) and post-transcriptionally stabilizing oncogenic proteins (e.g., inhibiting transcription of FBXW7, a tumor suppressor and E3 ligase targeting c-Myc for degradation). Additionally, ZC3H15 has been shown to regulate the NF-κB pathway via interaction with TRAF2. While there are no current drugs directly targeting ZC3H15, its role in cancer progression supports consideration as a future therapeutic target and prognostic biomarker.

Other names

DFRP1LEREPO4HSPC303HT010MSTP012PP730DRG family-regulatory protein 1Likely ortholog of mouse immediate early response erythropoietin 4