Skip to main content

MOLECULAR MECHANISMS OF LIVER SPECIFIC GENE EXPRESSION AND PRODUCTION OF PROTEINS OF MEDICAL INTEREST

Objective

SCIENTIFICALLY, A BETTER UNDERSTANDING OF THE TRANS-ACTING FACTORS WHICH MODIFY THE PROTEINS IN THE MAMMALIAN CELLS IS EXPECTED. THE APPLICATIONS ARE OBVIOUS : PRESENTLY THESE FACTORS ARE THE MAIN DIFFICULTY FOR THE OBTENTION OF CLONED PROTEINS HAVING THE RIGHT PHYSIOLOGICAL PROPERTIES.

THE OBTENTION OF NEW LIVER CELL LINES FOR CULTIVATION MIGHT ALSO BE AN IMPORTANT STEP TOWARD AN INDUSTRIAL APPLICATION.
Research has been carried out on the regulation of expression of genes expressed in hepatocytes with a view to production of blood proteins in hepatocyte derived mass cultures. Through analysis of transcription regulatory regions of 6 liver specific genes, it was discovered that the immediate 5' flanking regions contained sufficient information to ensure tissue specific expression, and to respond to inducers of the acute phase. Liver specificity can be attributed to the need for at least one hepatocyte specific transcription factor. The same factor, in various combinations with other liver or ubiquitous factors, guides the expression of a whole set of liver specific genes. This work provided background information to achieve molecular cloning of liver specific transcription factors. LF-B1/HNF1 is a homeobox containing protein, a class of proteins involved in early development. Cytokines, previously attributed to regulation of the immune response, are key elements in the induction of the acute phase response of liver.
RECENT EXPERIENCE HAS SHOWN THAT MICROBIAL "BIO-FACTORIES" MAY IN FACT SYNTHESIZE MOLECULES THAT HAVE NOT UNDERGONE ALL NECESSARY POST-TRANSATIONAL MODIFICATIONS. THIS PROJECT IS AIMED AT DEFINING THE SEQUENCES AND THE TRANS-ACTING FACTORS INVOLVED IN THE REGULATION OF EXPRESSION OF THE MAMMALS SERUM PROTEINS. IT WAS RECENTLY POSSIBLE TO DEFINE THE SEQUENCES WITH WHICH AT LEAST THREE DIFFERENT TRANS-ACTING FACTORS INTERACT. THE ANALYSIS WILL BE EXTENDED TO NEW GENES AND THE ISOLATION AND CLONING OF REGULATORY FACTORS WILL BE UNDERTAKEN.

THESE REGULATORY SEQUENCES WILL BE RECOMBINED WITH ONCO-GENES IN ORDER TO OBTAIN TRANSGENIC MICE THAT PRODUCE HEPATOMA AT DIFFERENT DEVELOPMENTAL STAGES : THIS WILL PROVIDE AN ORIGINAL SOURCE OF NEW CELL LINES.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

Università degli Studi di Napoli
Address
Via S. Pansini 5
80131 Napoli
Italy

Participants (2)

EUROPEAN MOLECULAR BIOLOGY LABORATORY
Germany
Address
Meyerhofstrasse 1
Heidelberg
Institut Pasteur
France
Address
28 Rue Du Docteur Roux
75724 Paris