NSC 663284 (DA3003-1), Cdc25 inhibitor

Supplementary information

This supplementary information is collated from multiple sources and compiled automatically.

The Cdc25 phosphatase family consisting of Cdc25A Cdc25B and Cdc25C plays key roles in controlling cell cycle progression. Cdc25A with a molecular mass of approximately 65 kDa is primarily located in the nucleus of proliferating cells. Cdc25B around 62 kDa can shuttle between the cytoplasm and nucleus and is often seen in various tissues including brain and testis. Cdc25C about 49 kDa mainly remains in the cytoplasm but translocates to the nucleus at specific cell cycle stages. KMT5A also known as SETD8 or Pr-SET7 is a histone methyltransferase with a molecular weight of approximately 41 kDa expressed in the nucleus of all proliferating cells.

Biological function summary

These Cdc25 proteins activate cyclin-dependent kinases (CDKs) by dephosphorylating key amino acids promoting cell cycle progression through different phases such as G1 S and G2/M. They are not part of a major complex but interact with cell cycle regulators and checkpoints. KMT5A specifically monomethylates histone H4 at lysine 20 (H4K20me1) affecting chromatin structure and regulating gene expression. This modification influences DNA replication and repair mechanisms.

Pathways

These proteins influence the cell cycle regulation and DNA damage response pathways. Cdc25 phosphatases interact closely with cyclin-CDK complexes driving cell cycle transitions. For example Cdc25A promotes G1/S transition in cooperation with CDK2. KMT5A is involved in DNA replication initiation and interacts with proteins like proliferating cell nuclear antigen (PCNA). It is also integral to damage response pathways ensuring genomic stability by interacting with replication licensing factors.

These targets have significant roles in cancer development and progression. Overexpression of Cdc25A and B is observed in various tumors linking them to malignancies such as breast and prostate cancer. They impact tumor progression by deregulating cell cycle checkpoints. Aberrant KMT5A expression and its influence on chromatin modification relate to disorders like tail chromosome instability syndrome. KMT5A’s interaction with proteins such as p53 connects it to tumor-suppressor pathways affected in cancer.