Molecular Dissection of the 8 Phase Transcriptional Program Controlled by Cyclin E/P220 NPAT Signaling Pathway
Abstract
Deregulation of the cyclin E pathway is associated with breast cancer. p220 links cyclin E to important S-phase events that are required for DNA replication, including induction of histone gene transcription. We examined the function of p220 through the development of human somatic HCTl 16 cells that conditionally express p220. We found that p220 is required for the transition from GO/Gi into S-phase, the activation of endogenous histone gene transcription, and the localization of Cajal body component p80(sub coilin) Expression of human papillomavirus E7 abrogated cell cycle arrest in response to p220-depletion, but not the defects in hi stone gene transcription activation. Basal histone 114 expression in GO/GI, although p220-dependent, occurs in the absence of detectable phosphorylation of p220 on Cdk2 sites. These findings indicate that p220 is an essential downstream component of the cyclin E/Cdk2 signaling pathway and functions to coordinate multiple elements of the Gl/S transition.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2004
- Accession Number
- ADA425741
Entities
People
- Grzegorz Nalepa
- Jeffrey Harper
Organizations
- Baylor College of Medicine