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Protein Arginine N-methyltransferase 2 (PRMT-2), a Modulator of NF-kappaB, E2F1, and STAT3 Activity

Posted Dec 31 2006 4:00pm

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 E Nabel (NHLBI)
Hiroaki Iwasaki (NHLBI)
Takanobu Yoshimoto (NHLBI)
Gary J Nabel (NIAID)


Patent Status:
HHS, Reference No. E-190-2003/0
US,


Licensing Status:
Available for exclusive or nonexclusive licensing.


Portfolios:
Internal Medicine
Internal Medicine - Diagnostics
Internal Medicine - Research Materials
Research Materials



For Additional Information Please Contact:
Suryanarayana Vepa Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: vepas@mail.nih.gov
Phone: 301-435-5020
Fax: 301-402-0220


Ref No: 742

Updated: 01/2007

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