This application describes the use of the N-terminal propiece of the lnterleukin-1 alpha precursor molecule for the specific induction of tumor cell apoptosis. No function has ever been attributed to this pro-piece fragment. We describe the mechanisms of cellular entry, nuclear targeting, inter-action with pre mRNA splicing factors, and modulation of alternative splicing of an apoptotic protein by the IL-1 alpha propiece. In addition, we demonstrate propiece interaction with important families of proteins modulating mitochondrial function. The result is tumor cell apoptosis. Importantly, normal diploid primary human cells do not undergo IL-1 alpha propiece-induced apoptosis. The IL-1 alpha propiece maybe delivered to cells either via an expression vector or as a peptide. In the latter case the propiece enters cells by a unique and non-saturable mechanism.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA092133-01A1
Application #
6477633
Study Section
Experimental Therapeutics Subcommittee 1 (ET)
Program Officer
Yovandich, Jason L
Project Start
2002-07-01
Project End
2005-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
1
Fiscal Year
2002
Total Cost
$276,281
Indirect Cost
Name
Northern California Institute Research & Education
Department
Type
DUNS #
City
San Francisco
State
CA
Country
United States
Zip Code
94121