Fizzy-related protein 1 (FZR1) (FZR1)

Fizzy-related protein 1 (FZR1), also known as Cdh1, is a crucial co-activator of the Anaphase-Promoting Complex/Cyclosome (APC/C), a multi-subunit E3 ubiquitin ligase [UniProt: Q9UM11]. It functions primarily during late mitosis and the G1 phase of the cell cycle, where it identifies and recruits specific substrates containing a destruction box (D-box) or KEN-box motif for ubiquitination and subsequent proteasomal degradation [PubMed: 25341468]. By regulating the stability of proteins such as Cyclin B1, Securin, and Skp2, FZR1 ensures the orderly exit from mitosis and maintains the G1 state to prevent premature DNA replication [PubMed: 21680707]. In the context of human disease, FZR1 is frequently characterized as a tumor suppressor; its loss or inactivation leads to genomic instability, aneuploidy, and accelerated cell cycle progression in various malignancies [PubMed: 21680707]. Additionally, FZR1 plays non-canonical roles in the nervous system, where it regulates axonal growth and synaptic plasticity, and its dysfunction has been linked to neurodegenerative conditions like Alzheimer's disease [PubMed: 23333473]. Although no FZR1-targeted therapies are currently FDA-approved, small-molecule inhibitors like Apcin have been developed to block the interaction between FZR1 and its substrates, serving as valuable tools for studying cell cycle control and potential anti-cancer strategies [PubMed: 24463511].

Other names

Cdh1FZRH-FZRCDC20-like protein 1FYR

Competitive inhibition of the D-box binding site on FZR1 to prevent substrate recruitment to the APC/C complex