Asset Details
Do you wish to reserve the book?
4E-BP1 is a target of Smad4 essential for TGFbeta-mediated inhibition of cell proliferation
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
4E-BP1 is a target of Smad4 essential for TGFbeta-mediated inhibition of cell proliferation
Do you wish to request the book?
4E-BP1 is a target of Smad4 essential for TGFbeta-mediated inhibition of cell proliferation
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
4E-BP1 is a target of Smad4 essential for TGFbeta-mediated inhibition of cell proliferation
2009
Overview
Assembly of the multi-subunit eukaryotic translation initiation factor-4F (eIF4F) is critical for protein synthesis and cell growth and proliferation. eIF4F formation is regulated by the translation-inhibitory protein 4E-BP1. While proliferation factors and intracellular pathways that impinge upon 4E-BP1 phosphorylation have been extensively studied, how they control 4E-BP1 expression remains unknown. Here, we show that Smad4, a transcription factor normally required for TGFbeta-mediated inhibition of normal cell proliferation, enhances 4E-BP1 gene-promoter activity through binding to a conserved element. 4E-BP1 expression is specifically modulated by treatment with TGFbeta and by manipulations of the natural Smad4 regulators (co-Smads) in cells isolated from Smad4(+/+) human tumours, whereas no response is observed in cells isolated from Smad4(-/-) human tumours or in cells where Smad4 has been knocked down by specific siRNAs. In addition, cells where 4E-BP1 has been knocked down (inducible shRNAs in human pancreatic cancer cells or siRNAs in non-malignant human keratinocytes) or has been knocked out (mouse embryonic fibroblasts isolated from 4E-BP1(-/-) mice) proliferate faster and are resistant to the antiproliferative effect of TGFbeta. Thus, 4E-BP1 gene appears critical for TGFbeta/Smad4-mediated inhibition of cell proliferation.
Publisher
EMBO Press
Subject
Adaptor Proteins, Signal Transducing
/ Adaptor Proteins, Signal Transducing - antagonists & inhibitors
/ Adaptor Proteins, Signal Transducing - genetics
/ Adaptor Proteins, Signal Transducing - physiology
/ Animals
/ Cell Proliferation - drug effects
/ Down-Regulation - drug effects
/ Gene Expression Regulation, Neoplastic
/ Gene Expression Regulation, Neoplastic - drug effects
/ Humans
/ Mice
/ Phosphoproteins - antagonists & inhibitors
/ Phosphoproteins - physiology
/ RNA, Small Interfering - pharmacology
/ Transforming Growth Factor beta
