Negative Regulation of DNA Replication by the Retinoblastoma Protein Is Mediated by Its Association with MCM7

Autor: Sterner, Jacqueline M., Dew-Knight, Susan, Musahl, Christine, Kornbluth, Sally, Horowitz, Jonathan M.
Zdroj: Molecular and Cellular Biology; May 1998, Vol. 18 Issue: 5 p2748-2757, 10p
Abstrakt: ABSTRACTA yeast two-hybrid screen was employed to identify human proteins that specifically bind the amino-terminal 400 amino acids of the retinoblastoma (Rb) protein. Two independent cDNAs resulting from this screen were found to encode the carboxy-terminal 137 amino acids of MCM7, a member of a family of proteins that comprise replication licensing factor. Full-length Rb and MCM7 form protein complexes in vitro, and the amino termini of two Rb-related proteins, p107 and p130, also bind MCM7. Protein complexes between Rb and MCM7 were also detected in anti-Rb immunoprecipitates prepared from human cells. The amino-termini of Rb and p130 strongly inhibited DNA replication in an MCM7-dependent fashion in a Xenopusin vitro DNA replication assay system. These data provide the first evidence that Rb and Rb-related proteins can directly regulate DNA replication and that components of licensing factor are targets of the products of tumor suppressor genes.
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