Project

Back to overview

Analysis of protein interactions linking a nuclear receptor with the TGFbeta pathway in the tissue-specific regulation of a retroviral promoter

English title Analysis of protein interactions linking a nuclear receptor with the TGFbeta pathway in the tissue-specific regulation of a retroviral promoter
Applicant Buetti Elena
Number 114127
Funding scheme Project funding
Research institution Institut de Microbiologie - CHUV Faculté de Biologie et Médecine Université de Lausanne
Institution of higher education University of Lausanne - LA
Main discipline Experimental Microbiology
Start/End 01.02.2007 - 31.01.2009
Approved amount 125'800.00
Show all

Keywords (6)

mouse mammary tumor virus; steroid hormone receptors; ETS transcription factors; transforming growth factor beta; protein kinase C; Src kinases

Lay Summary (English)

Lead
Lay summary
Retroviruses insert a DNA copy of their genome into that of the host cell, and exploit the cellular machinery for their replication. They are therefore excellent tools for studying basic cellular regulatory mechanisms. The Mouse Mammary Tumor Virus (MMTV) is transmitted through the milk and infects first B-lymphocytes in the intestinal wall. It is via lymphocytes that it reaches and infects the mammary gland, where it is highly produced under the influence of pregnancy hormones, and eventually causes carcinomas. MMTV is a prime model for studying the effects of hormones and of the cell-specific environment on the activity of genes. Because of their crucial role in the infection process, we are studying MMTV expression in mouse B-lymphocytes in culture, using methods of molecular biology and biochemistry. Our studies allowed the discovery of a novel combination of cellular regulatory signals involving the glucocorticoid hormone receptor, the cytokine Transforming Growth Factor beta (TGF beta), through its transcriptional mediators Smads, and the transcription factor GABP, all three binding in close proximity to the MMTV promoter DNA. While analyzing the signaling pathways regulating this transcriptional complex, we found a differential requirement for the enzyme protein kinase C delta, both for the glucocorticoid hormone response and for a synergism between hormone and TGF beta. The latter was also regulated by another protein kinase belonging to the family of Src oncogenes. We also showed various intracellular associations between the different factors and kinases, supporting their functional connections. Our results define a novel combination of intracellular pathways, allowing a fine-tuning of the response to multiple extracellular signals. These mechanisms may be also used for important cellular genes, as the molecules involved play key roles in proliferative, inflammatory, and immune processes.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Name Institute

Employees

Associated projects

Number Title Start Funding scheme
102093 Dissection of signaling pathways and transcription factor interactions regulating a model viral promoter in a cell-type specific way 01.11.2003 Project funding

-