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PMID: 9566894 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Molecular and cellular biology ·Vol. 18 ·No. 5 ·1998-05-00 ·Pages 2748-57

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

Abstract

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.

MeSH Terms
Amino Acid Sequence Animals Cell Cycle Proteins DNA Replication DNA, Complementary/genetics DNA-Binding Proteins/genetics,metabolism Humans Male Minichromosome Maintenance Complex Component 7 Molecular Sequence Data Nuclear Proteins/genetics,metabolism Ovum Peptide Fragments/genetics,metabolism Phosphoproteins/metabolism Protein Binding Proteins Recombinant Proteins/metabolism Retinoblastoma Protein/genetics,metabolism Retinoblastoma-Like Protein p107 Retinoblastoma-Like Protein p130 Spermatozoa Xenopus Xenopus Proteins
Chemicals
Cell Cycle Proteins DNA, Complementary DNA-Binding Proteins Nuclear Proteins Peptide Fragments Phosphoproteins Proteins RBL1 protein, human RBL2 protein, human Recombinant Proteins Retinoblastoma Protein Retinoblastoma-Like Protein p107 Retinoblastoma-Like Protein p130 Xenopus Proteins MCM7 protein, human Mcm7 protein, Xenopus Minichromosome Maintenance Complex Component 7
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Sterner J M
Department of Molecular Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Dew-Knight S
Musahl C
Kornbluth S
Horowitz J M
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.18.5.2748
Published
1998-05-00
Pages
2748-57
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC110654
Subset
IM
Grants
NCI NIH HHS · CA53248 · United States
External Links
PubMed source DOI: 10.1128/MCB.18.5.2748 PMC Full Text View journal details
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