Protein Arginine N-methyltransferase 2 (PRMT-2), a Modulator of NF-kappaB, E2F1, and STAT3 Activity
Description of Invention:
Protein-arginine methyltransferases (PRMTs) contain methyltransferase domains that modify chromatin and regulate cellular transcription through the post-translational methylation of arginine residues on the guanidine group of target proteins. Members of this family have roles in RNA processing, transcriptional regulation, signal transduction, and DNA repair. Until recently, the functional significance of one member of this family, PRMT-2, was unknown.
Researchers at NHLBI, led by Dr. Elizabeth Nabel, have elucidated the role of PRMT-2. They have found that PRMT-2 modulates the activity of NF-kappaB, E2F1, and STAT3. PRMT-2 inhibits NF-kappaB dependent transcription, and therefore PRMT-2 has a role in modulating inflammation and the immune response. Also, PRMT-2 proteins can repress E2F1 transcriptional activity and cause cell cycle arrest, and thus may be used to treat or prevent cancer. PRMT-2 also methylates STAT3, and inhibition or loss of PRMT-2 function causes mammals to lose weight, eat less and become more sensitive to insulin.
The invention describes methods of modulating PRMT-2 activity or expression in cells. These methods can be used to inhibit the function of NF-kappaB, E2F1 and STAT3 for treatment of a number of disorders, including inflammation, cancer, and diabetes.
Applications:
Target for treatment and study of a number of disorders, including:
Diabetes, obesity and metabolic syndrome diseases
Inflammation and immune response-related disorders
Cancer
Inventors:
Elizabeth Nabel (NHLBI) Hiroaki Iwasaki (NHLBI) Takanobu Yoshimoto (NHLBI) and Gary Nabel (NIAID)
Patent Status:
DHHS Reference No. E-190-2003/0 --
U.S. Provisional Application No. 60/466,751 filed 30 Apr 2003
PCT Application No. PCT/US2004/13375 filed 30 Apr 2004, which published as WO 2004/098634 on 18 Nov 2004
U.S. Patent Application No. 11/263,657 filed 31 Oct 2005, which published as WO 2006/0239990 on 26 Oct 2006
Licensing Status: Available for exclusive or nonexclusive licensing.
For Additional Information Please Contact: Tara L. Kirby Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301)435-4426
Email: tarak@mail.nih.gov
Fax: (301)402-0220
