Fizzy-related protein homolog (FZR1)

Fizzy-related protein homolog (FZR1) is a substrate-specific adaptor protein for the anaphase-promoting complex/cyclosome (APC/C), playing an essential role in the controlled degradation of cell cycle regulators to ensure proper progression through mitosis and maintenance of genomic stability[1][2]. FZR1 associates with APC/C following CDC20 dissociation in late mitosis and promotes the ubiquitination of substrates such as cyclin B and securin, allowing correct anaphase initiation and mitotic exit[1][2]. Phosphorylation cycles regulate FZR1 activity, especially at the G1/S checkpoint and in response to DNA damage, where it is implicated in halting mitotic progression and promoting DNA repair[1][2]. Beyond its cell cycle functions, FZR1/CDH1 regulates neurodevelopment, controlling neuronal survival, axonal outgrowth, and synapse function[4]. Pathogenic mutations in FZR1 result in developmental and epileptic encephalopathy and associations with neurodevelopmental disorders, while altered expression or dysregulation is implicated in cancer and other diseases[2][4]. Research targeting FZR1 for therapeutics is ongoing, with diagnostic and prognostic biomarker potential in oncology and neurology[2][4].

Other names

CDH1FYRFZRKIAA1242HCDH1CDC20CCDC20-like protein 1Cdh1/Hct1 homologCDC20 homolog 1DEE109CDC20-like 1bHCDHfizzy/cell division cycle 20 related 1FZR2retina aberrant in pattern (rap), in Drosophila

Modulators of FZR1 would affect APC/C-mediated ubiquitination leading to altered degradation of cell cycle regulators such as cyclin B and securin, potentially inducing cell-cycle arrest or apoptosis in cancer cells[2]. Indirect regulation of DNA damage response via partnership with p53 and ubiquitination of downstream effectors[1][2].