Open AccessRegulation of RB Transcription In Vivo by RB Family Members
Author(s) -
Deborah L. Burkhart,
Lynn K. Ngai,
Caitlin M. Roake,
Patrick Viatour,
Chellappagounder Thangavel,
Victoria M. Ho,
Erik S. Knudsen,
Julien Sage
Publication year - 2010
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.00952-09
Subject(s) - biology , e2f , cyclin d1 , microbiology and biotechnology , retinoblastoma protein , retinoblastoma , transcription (linguistics) , transcription factor , e2f1 , transgene , reporter gene , gene , cell cycle , genetics , gene expression , linguistics , philosophy
In cancer cells, the retinoblastoma tumor suppressor RB is directly inactivated by mutation in theRB gene or functionally inhibited by abnormal activation of cyclin-dependent kinase activity. While variations inRB levels may also provide an important means of controlling RB function in both normal and cancer cells, little is known about the mechanisms regulatingRB transcription. Here we show that members of the RB and E2F families bind directly to theRB promoter. To investigate how the RB/E2F pathway may regulateRb transcription, we generated reporter mice carrying aneGFP transgene inserted into a bacterial artificial chromosome containing most of theRb gene. Expression of eGFP largely parallels that ofRb in transgenic embryos and adult mice. Using these reporter mice and mutant alleles forRb ,p107 , andp130 , we found that RB family members modulateRb transcription in specific cell populationsin vivo and in culture. Interestingly, whileRb is a target of the RB/E2F pathway in mouse and human cells,Rb expression does not strictly correlate with the cell cycle status of these cells. These experiments identify novel regulatory feedback mechanisms within the RB pathway in mammalian cells.