Checkpoint with forkhead and ring finger domains (E3 ubiquitin-protein ligase CHFR) (CHFR)

The checkpoint with forkhead and ring finger domains (CHFR) is a multifunctional, tumor suppressor protein characterized as an E3 ubiquitin-protein ligase. CHFR plays a critical role in regulating the cell cycle by acting as an early mitotic checkpoint—delaying progression into mitosis in response to mitotic stress, especially from microtubule-interfering agents like taxanes. The protein contains a forkhead-associated (FHA) domain, a RING finger (RF) domain, and a cysteine-rich region, each conferring specific functional properties. CHFR promotes the ubiquitination and proteasomal degradation of several key regulators of mitosis, including PLK1 and Aurora A. Loss or silencing (often by promoter methylation) of CHFR is frequent in a range of human cancers and is associated with defective checkpoint function, enhanced genomic instability, and increased sensitivity to microtubule-targeting chemotherapeutics, making it both a drug-response biomarker and a putative therapeutic target[1][2][3].

Other names

E3 ubiquitin-protein ligase CHFRRNF196FLJ10796RING finger protein 196RING-type E3 ubiquitin transferase CHFRcheckpoint with forkhead and RING finger domains protein

Drugs increase efficacy when CHFR expression is lost (e.g., taxanes induce mitotic arrest more effectively in CHFR-deficient cells) Targeting the degradation of CHFR substrates (Aurora A, PLK1) by enhancing their accumulation or breakdown