Negative regulation of DNA replication by the retinoblastoma protein is mediated by its association with MCM7.

Published

Journal Article

A 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 Xenopus in 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.

Full Text

Duke Authors

Cited Authors

  • Sterner, JM; Dew-Knight, S; Musahl, C; Kornbluth, S; Horowitz, JM

Published Date

  • May 1998

Published In

Volume / Issue

  • 18 / 5

Start / End Page

  • 2748 - 2757

PubMed ID

  • 9566894

Pubmed Central ID

  • 9566894

Electronic International Standard Serial Number (EISSN)

  • 1098-5549

International Standard Serial Number (ISSN)

  • 0270-7306

Digital Object Identifier (DOI)

  • 10.1128/mcb.18.5.2748

Language

  • eng