Molecular Dissection of the 8 Phase Transcriptional Program Controlled by Cyclin E-P220 NPAT Signaling Pathway
Abstract
Cyclin E/Cdk2, a central regulator of the G1/S transition, coordinates multiple cell cycle events, including DNA replication, centrosome duplication, and activation of the E2F transcriptional program. Recent studies suggest a role for cyclin E/Cdk2 in activation of histone transcription during S phase via the Cajal body-associated protein p22ONPAT, and in addition, p220 can promote S-phase entry independently of histone transcriptional activation when overexpressed. We found that p220 is required for proliferation of HCT116 cells, as assessed after expression of Cre recombinase in p220fl0x/-cells. This defect was due to an inability of these cells to transit from 00/01 into S phase, and cell cycle arrest occurred in the presence of elevated Cdk2 kinase activity. Expression of human papillomavirus E7, but not E6, eliminated cell cycle arrest in response to p220 depletion. Optimal expression of all four core histone genes required p220. Basal histone H4 expression in G0/G1, although p220-dependent, occurs in the absence of detectable phosphorylation of p220 on Cdk2 sites. These finding indicate that p220 is an essential downstream component of the cyclin E/Cdk2 signaling pathway and functions to coordinate multiple elements of the G1/S transition.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2005
- Accession Number
- ADA437629
Entities
People
- Grzegorz Nalepa
- Jeffrey Harper
Organizations
- Baylor College of Medicine