Ret finger protein-like 3 (RFPL3)

Ret finger protein-like 3 (RFPL3) is a human gene located at chromosome 22q12.3 encoding a zinc-finger regulatory protein with ubiquitin ligase activity. RFPL3 is notable for binding to the hTERT promoter (the gene encoding the active subunit of telomerase) and, in cooperation with CBP, upregulating hTERT transcription and enhancing telomerase activity—mechanisms crucial for oncogenesis and tumor cell proliferation in lung cancer. RFPL3 lacks a canonical DNA-binding domain but contains several protein-protein interaction domains, enabling it to act as a transcriptional co-regulator by recruiting partners to gene promoters. Increased RFPL3 expression is correlated with poor prognosis and increased metastasis in cancer patients, making it a promising but experimental therapeutic target for molecular oncology. There are no approved drugs targeting RFPL3 as of 2025; current research involves gene silencing approaches in preclinical models.

Other names

RNF120Ret finger protein-like 3RFPL3

Inhibition: RNAi/shRNA used to suppress RFPL3 expression decreases hTERT activity and tumor cell growth. Indirect: targeting RFPL3 affects transcriptional activation of hTERT, a key oncogenic driver.