Cdc6 is regulated by E2F and is essential for DNA replication in mammalian cells.

Published

Journal Article

Cdc6 has a critical regulatory role in the initiation of DNA replication in yeasts, but its function in mammalian cells has not been characterized. We show here that Cdc6 is expressed selectively in proliferating but not quiescent mammalian cells, both in culture and within tissues of intact animals. During the transition from a growth-arrested to a proliferative state, transcription of mammalian Cdc6 is regulated by E2F proteins, as revealed by a functional analysis of the human Cdc6 promoter and by the ability of exogenously expressed E2F proteins to stimulate the endogenous Cdc6 gene. Immunodepletion of Cdc6 by microinjection of anti-Cdc6 antibody blocks initiation of DNA replication in a human tumor cell line. We conclude that expression of human Cdc6 is regulated in response to mitogenic signals though transcriptional control mechanisms involving E2F proteins, and that Cdc6 is required for initiation of DNA replication in mammalian cells.

Full Text

Duke Authors

Cited Authors

  • Yan, Z; DeGregori, J; Shohet, R; Leone, G; Stillman, B; Nevins, JR; Williams, RS

Published Date

  • March 31, 1998

Published In

Volume / Issue

  • 95 / 7

Start / End Page

  • 3603 - 3608

PubMed ID

  • 9520412

Pubmed Central ID

  • 9520412

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.95.7.3603

Language

  • eng

Conference Location

  • United States