Regulation of RB transcription in vivo by RB family members

Deborah L. Burkhart, Lynn K. Ngai, Caitlin M. Roake, Patrick Viatour, Chellappagounder Thangavel, Victoria M. Ho, Erik S. Knudsen, Julien Sage

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

In cancer cells, the retinoblastoma tumor suppressor RB is directly inactivated by mutation in the RB gene or functionally inhibited by abnormal activation of cyclin-dependent kinase activity. While variations in RB levels may also provide an important means of controlling RB function in both normal and cancer cells, little is known about the mechanisms regulating RB transcription. Here we show that members of the RB and E2F families bind directly to the RB promoter. To investigate how the RB/E2F pathway may regulate Rb transcription, we generated reporter mice carrying an eGFP transgene inserted into a bacterial artificial chromosome containing most of the Rb gene. Expression of eGFP largely parallels that of Rb in transgenic embryos and adult mice. Using these reporter mice and mutant alleles for Rb, p107, and p130, we found that RB family members modulate Rb transcription in specific cell populations in vivo and in culture. Interestingly, while Rb 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.

Original languageEnglish (US)
Pages (from-to)1729-1745
Number of pages17
JournalMolecular and Cellular Biology
Volume30
Issue number7
DOIs
StatePublished - Apr 2010

Fingerprint

Retinoblastoma Genes
Bacterial Artificial Chromosomes
Neoplasms
Cyclin-Dependent Kinases
Retinoblastoma
Transgenes
Cell Cycle
Embryonic Structures
Alleles
Mutation
Population
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Burkhart, D. L., Ngai, L. K., Roake, C. M., Viatour, P., Thangavel, C., Ho, V. M., ... Sage, J. (2010). Regulation of RB transcription in vivo by RB family members. Molecular and Cellular Biology, 30(7), 1729-1745. https://doi.org/10.1128/MCB.00952-09

Regulation of RB transcription in vivo by RB family members. / Burkhart, Deborah L.; Ngai, Lynn K.; Roake, Caitlin M.; Viatour, Patrick; Thangavel, Chellappagounder; Ho, Victoria M.; Knudsen, Erik S.; Sage, Julien.

In: Molecular and Cellular Biology, Vol. 30, No. 7, 04.2010, p. 1729-1745.

Research output: Contribution to journalArticle

Burkhart, DL, Ngai, LK, Roake, CM, Viatour, P, Thangavel, C, Ho, VM, Knudsen, ES & Sage, J 2010, 'Regulation of RB transcription in vivo by RB family members', Molecular and Cellular Biology, vol. 30, no. 7, pp. 1729-1745. https://doi.org/10.1128/MCB.00952-09
Burkhart DL, Ngai LK, Roake CM, Viatour P, Thangavel C, Ho VM et al. Regulation of RB transcription in vivo by RB family members. Molecular and Cellular Biology. 2010 Apr;30(7):1729-1745. https://doi.org/10.1128/MCB.00952-09
Burkhart, Deborah L. ; Ngai, Lynn K. ; Roake, Caitlin M. ; Viatour, Patrick ; Thangavel, Chellappagounder ; Ho, Victoria M. ; Knudsen, Erik S. ; Sage, Julien. / Regulation of RB transcription in vivo by RB family members. In: Molecular and Cellular Biology. 2010 ; Vol. 30, No. 7. pp. 1729-1745.
@article{2a03b475559648869dd814ede8244975,
title = "Regulation of RB transcription in vivo by RB family members",
abstract = "In cancer cells, the retinoblastoma tumor suppressor RB is directly inactivated by mutation in the RB gene or functionally inhibited by abnormal activation of cyclin-dependent kinase activity. While variations in RB levels may also provide an important means of controlling RB function in both normal and cancer cells, little is known about the mechanisms regulating RB transcription. Here we show that members of the RB and E2F families bind directly to the RB promoter. To investigate how the RB/E2F pathway may regulate Rb transcription, we generated reporter mice carrying an eGFP transgene inserted into a bacterial artificial chromosome containing most of the Rb gene. Expression of eGFP largely parallels that of Rb in transgenic embryos and adult mice. Using these reporter mice and mutant alleles for Rb, p107, and p130, we found that RB family members modulate Rb transcription in specific cell populations in vivo and in culture. Interestingly, while Rb 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.",
author = "Burkhart, {Deborah L.} and Ngai, {Lynn K.} and Roake, {Caitlin M.} and Patrick Viatour and Chellappagounder Thangavel and Ho, {Victoria M.} and Knudsen, {Erik S.} and Julien Sage",
year = "2010",
month = "4",
doi = "10.1128/MCB.00952-09",
language = "English (US)",
volume = "30",
pages = "1729--1745",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "7",

}

TY - JOUR

T1 - Regulation of RB transcription in vivo by RB family members

AU - Burkhart, Deborah L.

AU - Ngai, Lynn K.

AU - Roake, Caitlin M.

AU - Viatour, Patrick

AU - Thangavel, Chellappagounder

AU - Ho, Victoria M.

AU - Knudsen, Erik S.

AU - Sage, Julien

PY - 2010/4

Y1 - 2010/4

N2 - In cancer cells, the retinoblastoma tumor suppressor RB is directly inactivated by mutation in the RB gene or functionally inhibited by abnormal activation of cyclin-dependent kinase activity. While variations in RB levels may also provide an important means of controlling RB function in both normal and cancer cells, little is known about the mechanisms regulating RB transcription. Here we show that members of the RB and E2F families bind directly to the RB promoter. To investigate how the RB/E2F pathway may regulate Rb transcription, we generated reporter mice carrying an eGFP transgene inserted into a bacterial artificial chromosome containing most of the Rb gene. Expression of eGFP largely parallels that of Rb in transgenic embryos and adult mice. Using these reporter mice and mutant alleles for Rb, p107, and p130, we found that RB family members modulate Rb transcription in specific cell populations in vivo and in culture. Interestingly, while Rb 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.

AB - In cancer cells, the retinoblastoma tumor suppressor RB is directly inactivated by mutation in the RB gene or functionally inhibited by abnormal activation of cyclin-dependent kinase activity. While variations in RB levels may also provide an important means of controlling RB function in both normal and cancer cells, little is known about the mechanisms regulating RB transcription. Here we show that members of the RB and E2F families bind directly to the RB promoter. To investigate how the RB/E2F pathway may regulate Rb transcription, we generated reporter mice carrying an eGFP transgene inserted into a bacterial artificial chromosome containing most of the Rb gene. Expression of eGFP largely parallels that of Rb in transgenic embryos and adult mice. Using these reporter mice and mutant alleles for Rb, p107, and p130, we found that RB family members modulate Rb transcription in specific cell populations in vivo and in culture. Interestingly, while Rb 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.

UR - http://www.scopus.com/inward/record.url?scp=77949408525&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77949408525&partnerID=8YFLogxK

U2 - 10.1128/MCB.00952-09

DO - 10.1128/MCB.00952-09

M3 - Article

VL - 30

SP - 1729

EP - 1745

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 7

ER -