Description of Invention:
This application relates to the field of apoptosis, in particular the application relates to a novel gene product which is associated with induction of apoptosis by Transforming Growth Factor Beta (TGF-beta). Apoptosis is a critical event in developmental processes and homeostasis; its dysregulation is often central to pathogenic mechanisms. Apoptotic aberrations contribute to the development of the transformed phenotype; both metastatic potential and tumor aggressiveness are associated with increased resistance to apoptosis. Certain chemotherapeutic agents act by increasing the sensitivity of cells to apoptosis and patients with mutations in genes regulating apoptosis are known to have a poor prognosis.
The application describes the cloning of a gene which encodes a splice variant of the known gene designated H5/PNUTL2/CDCrel-2a/2b and the isolation and characterization of its protein product. The newly identified protein, designated ARTS (Apoptosis Related Protein in the TGF-beta Signaling Pathway), is a member of the septin family of proteins. It is localized to mitochondria and translocates to the nucleus where ARTS induces apoptosis in response to TGF-beta. ARTS is the first septin shown to be essential for mediating TGF-beta dependent apoptosis. Antisense ARTS nucleic acids are also contemplated. Because of its role in regulating the sensitivity of cells to TGF-beta induced apoptosis ARTS derived products may provide a means for treating conditions where increased TGF-beta induced apoptosis is desired (e.g., cancer) and where decreased TGF-beta induced apoptosis is desired (e.g., neurodegenerative diseases).
Inventors:
Sarit Larisch-Bloch et al. (NCI)
Patent Status:
DHHS Reference No. E-062-2000/2 --
U.S. Patent Application No. 10/208,304 filed 29 Jul 2002, claiming priority to 29 Jan 2000
Relevant Publication: S Larisch-Bloch et al. Selective loss of the transforming growth factor-beta apoptotic signaling pathway in mutant NRP-154 rat prostatic epithelial cells. Cell Growth Differ. 2000 Jan;11(1):1-10. [PubMed abs]
Portfolios: Gene Based Therapies Central Nervous System Cancer
Cancer -Therapeutics-Gene Therapy-Genes Cancer -Therapeutics-Biological Response Modifiers-Cytokines Gene Based Therapies -Therapeutics-Gene Therapy-Therapeutic Genes Cancer -Therapeutics Central Nervous System -Therapeutics Gene Based Therapies -Therapeutics
For Additional Information Please Contact: Betty Tong Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: 301/594-6565
Email: tongb@mail.nih.gov
Fax: 301/402-0220
