CHFR
Description
The CHFR (checkpoint with forkhead and ring finger domains) is a protein-coding gene located on chromosome 12.
The CHFR gene encodes an E3 ubiquitin-protein ligase called CHFR, which plays a role in the DNA damage response and is recruited to sites of DNA damage. CHFR is crucial for the survival of male premeiotic germ cells. Approximately 30% of male CHFR knockout mice are infertile, exhibiting delayed spermatogenesis onset and increased apoptosis in premeiotic germ cells. These mice experience a complete loss of germ cells in their testes by the age of 3 months.
CHFR is an E3 ubiquitin ligase that acts in the antephase checkpoint, delaying entry into mitosis in response to microtubule poisons. It functions in early prophase, before chromosome condensation, when centrosomes move apart. CHFR likely signals the presence of mitotic stress caused by microtubule poisons by mediating Lys-48-linked ubiquitination of target proteins, leading to their degradation by the proteasome. It promotes the ubiquitination and subsequent degradation of AURKA and PLK1. CHFR potentially acts as a tumor suppressor, possibly by mediating the polyubiquitination of HDAC1, leading to its degradation. It may also promote the formation of Lys-63-linked polyubiquitin chains and functions with the specific ubiquitin-conjugating UBC13-MMS2 (UBE2N-UBE2V2) heterodimer. Substrates ubiquitinated at Lys-63 are typically not targeted for degradation but are involved in signaling cellular stress.
CHFR is also known as RNF116, RNF196.
