CDT2containing

CDT2-containing refers to protein complexes that include the CDT2 protein, most notably the CRL4-CDT2 E3 ubiquitin ligase complex. In this context, CDT2 serves as the substrate receptor (DCAF) for a CRL4 (CUL4–DDB1) ligase that can use either CUL4A or CUL4B and is associated with Rbx1. The complex is recruited to chromatin and is regulated in part by proliferating cell nuclear antigen (PCNA), which binds substrates containing PIP-box or related degron motifs.

The primary role of CDT2-containing complexes is targeted proteolysis of key cell cycle and DNA damage response proteins. Substrates include CDT1, p21, SETD8, and other factors involved in replication licensing and chromatin remodeling. Degradation typically occurs when PCNA is loaded onto DNA during S phase or in response to DNA damage, ensuring proper progression through replication and preventing re-replication or genome instability.

Biological significance of CDT2-containing CRL4 complexes lies in their contribution to genome stability and cell cycle control. By coordinating timely degradation of licensing factors and damage response proteins, they help maintain faithful replication and proper checkpoint function. Disruption of CDT2-containing ligases can lead to rereplication, replication stress, and defects in development or tumor suppression.

Regulation of CDT2-containing ligases involves cell cycle–dependent expression, post-translational modifications, and interactions with PCNA and chromatin. Dysregulation of these complexes has been observed in various cancers, making them a subject of interest for potential therapeutic strategies.

See also: CRL4 E3 ubiquitin ligases, CDT1, p21, PCNA, ubiquitin–proteasome system.