Direct control of cell cycle gene expression by proto-oncogene product ACTR, and its autoregulation underlies its transforming activity.

Molecular and Cellular Biology
Maggie C LouieHong-Wu Chen

Abstract

ACTR (also called AIB1 and SRC-3) was identified as a coactivator for nuclear receptors and is linked to multiple types of human cancer due to its frequent overexpression. However, the molecular mechanism of ACTR oncogenicity and its function independent of nuclear receptors remain to be defined. We demonstrate here that ACTR is required for both normal and malignant human cells to effectively enter S phase. RNA interference-mediated depletion and chromatin immunoprecipitation assays show that endogenous ACTR directly controls the expression of genes important for initiation of DNA replication, which include cdc6, cdc25A, MCM7, cyclin E, and Cdk2. Moreover, consistent with its critical role in cell cycle control, ACTR expression appears to be cell cycle regulated, which involves E2F. Interestingly, ACTR is recruited to its own promoter at the G1/S transition and activates its own expression, suggesting a positive feedback mechanism for ACTR action in the control of cell cycle progression and for its aberrant expression in cancers. Importantly, overexpression of ACTR alone transforms human mammary epithelial cells, which requires its association with E2F. These findings reveal a novel role for ACTR in cell cycle control and supp...Continue Reading

References

Sep 15, 1995·Science·K GalaktionovD Beach
Nov 1, 1996·Nucleic Acids Research·D TroucheT Kouzarides
Feb 17, 2000·The EMBO Journal·M A Martínez-BalbásT Kouzarides
Jun 22, 2000·International Journal of Cancer. Journal International Du Cancer·C SakakuraH Yamagishi
Jun 24, 2000·Molecular and Cellular Biology·J Font de Mora, M Brown
Jul 8, 2000·Proceedings of the National Academy of Sciences of the United States of America·M W StrobeckE S Knudsen
Oct 6, 2000·Genes & Development·J W Harbour, D C Dean
Nov 23, 2000·Proceedings of the National Academy of Sciences of the United States of America·Z WangM G Rosenfeld
Mar 21, 2001·Human Molecular Genetics·J R Nevins
Jun 19, 2001·International Journal of Cancer. Journal International Du Cancer·I R BukholmJ M Nesland
Jun 22, 2001·The Journal of Biological Chemistry·S E LangP Hearing
Aug 3, 2001·Nature·S J NielsenT Kouzarides
Dec 19, 2001·British Journal of Cancer·V J GnanapragasamC N Robson
Jan 19, 2002·Genes & Development·Bing RenBrian David Dynlacht
Feb 2, 2002·Nature Reviews. Molecular Cell Biology·Jeffrey M Trimarchi, Jacqueline A Lees
Jul 9, 2002·Molecular and Cellular Biology·Akihide RyoKun Ping Lu
Feb 18, 2003·Proceedings of the National Academy of Sciences of the United States of America·Maggie C LouieHong-Wu Chen
May 3, 2003·Cancer Cell·Hugh Cam, Brian David Dynlacht
May 16, 2003·Molecular and Cellular Biology·Paloma H GiangrandeJoseph R Nevins
Jan 20, 2004·Molecular and Cellular Biology·Hyeog KangKeji Zhao
Feb 7, 2004·The EMBO Journal·Slimane Ait-Si-AliAnnick Harel-Bellan
Feb 11, 2004·Endocrine Reviews·Carolyn L Smith, Bert W O'Malley
Mar 12, 2004·The EMBO Journal·Paloma H GiangrandeJoseph R Nevins
May 6, 2004·Journal of Cell Science·Maxim V Frolov, Nicholas J Dyson
Jul 14, 2004·Proceedings of the National Academy of Sciences of the United States of America·Tobias N DechowJacqueline F Bromberg
Aug 4, 2004·Proceedings of the National Academy of Sciences of the United States of America·Wenlin ShaoMyles Brown

❮ Previous
Next ❯

Citations

Feb 10, 2009·International Journal of Colorectal Disease·Petros D GrivasHaralabos Kalofonos
May 7, 2009·Breast Cancer Research and Treatment·Tyler LahusenAnna T Riegel
Aug 25, 2009·Nature Reviews. Cancer·Jianming XuBert W O'Malley
Dec 26, 2008·Proceedings of the National Academy of Sciences of the United States of America·Shu WangJianming Xu
Sep 22, 2010·Molecular and Cellular Biology·Alexey S RevenkoHong-Wu Chen
Dec 14, 2011·PloS One·Macarena FerreroJaime Font de Mora
Jun 8, 2011·International Journal of Biological Sciences·Gang MaJianjun He
Nov 14, 2007·Proceedings of the National Academy of Sciences of the United States of America·June X ZouHong-Wu Chen
Jun 12, 2014·FEBS Open Bio·Cecilia Viviana AlvaradoMónica Alejandra Costas
Aug 1, 2006·Biochemical and Biophysical Research Communications·Percy Luk YeungJ Don Chen
May 20, 2015·Biochimica Et Biophysica Acta·Olivera BozickovicJørn V Sagen
Feb 7, 2012·Biochimica Et Biophysica Acta·María F RubioMónica A Costas
Aug 14, 2015·Scientific Reports·Fatemeh FekrmandiJohn H White
Sep 12, 2006·FEBS Letters·Alvaro AvivarJaime Font de Mora
Jul 20, 2019·Endocrine, Metabolic & Immune Disorders Drug Targets·Athina ChasapiGeorgia Sotiropoulou-Bonikou
Apr 22, 2015·Oncoscience·Vineesh Indira ChandranMarie Ranson
Feb 4, 2010·Molecular Cancer Research : MCR·Elaine Y C HsiaHong-Wu Chen
Mar 11, 2010·Molecular Cancer Research : MCR·Maggie C LouieLauren Kawabata
Mar 25, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Line L Haugan MoiGunnar Mellgren
Mar 21, 2007·Cellular Signalling·Shaosi Li, Yongfeng Shang

❮ Previous
Next ❯

Related Concepts

Related Feeds