Negative regulation of DNA replication by the retinoblastoma protein is mediated by its association with MCM7.
Journal Article (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
- PMC110654
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