CDH1

Cdh1 is a regulatory co-activator of the anaphase-promoting complex/cyclosome (APC/C), a large multi-subunit E3 ubiquitin ligase that drives orderly progression through mitosis and the G1 phase. In many organisms, Cdh1 (also called Fizzy-related protein 1 in vertebrates and Hct1 in budding yeast) binds APC/C and changes its substrate specificity to promote degradation of key cell-cycle proteins during late mitosis and in G1. In humans, the APC/C co-activator is encoded by FZR1, and this protein is distinct from CDH1, the gene that encodes the cell‑cell adhesion protein E‑cadherin.

Function and mechanism

APC/C-Cdh1 targets a range of cell-cycle regulators for ubiquitination and proteasomal degradation. This activity facilitates mitotic exit and helps maintain G1 by preventing premature entry into S phase. Well-established substrates include mitotic cyclins (such as Cyclin B1) and other factors that promote cell-cycle progression and DNA replication licensing, as well as Geminin, a regulator of DNA replication. Through this degradation program, Cdh1 helps reset the cell cycle after division and supports genomic stability.

Regulation

Cdh1 activity is tightly controlled by phosphorylation. Cyclin-dependent kinase (CDK) activity during S, G2, and early M keeps Cdh1 phosphorylated and inactive; at the end of mitosis and into G1, dephosphorylation activates Cdh1 and enables APC/C binding. The activity is further modulated by regulatory proteins and timing within the cell-cycle network to ensure substrates are degraded in the proper window.

Biological and clinical relevance

Cdh1 is essential for proper mitotic exit, maintenance of G1, and overall genomic stability. Disruption of APC/C-Cdh1 function can contribute to abnormal cell-cycle progression and has been linked to diseases, including cancer, in certain contexts. Because CDH1 also denotes a different protein, E-cadherin, care is needed to distinguish these two genes in literature.