Just because Dr. Goeddel edited this doesn't mean Tularik isn't involved, but maybe it is?
>>Published online before print April 3, 2003
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0737244100
Microbiology
A secreted high-affinity inhibitor of human TNF from Tanapox virus
Craig R. Brunetti *, Mini Paulose-Murphy , Rajkumari Singh *, Jing Qin *, John W. Barrett *, Aubry Tardivel , Pascal Schneider , Karim Essani , and Grant McFadden *¶||
*BioTherapeutics Group, Robarts Research Institute, 1400 Western Road, London, ON, Canada N6G 2V4; ¶Department of Microbiology and Immunology, University of Western Ontario, London, ON, Canada N6A 5C1; Institute of Biochemistry, BIL Biomedical Research Center, University of Lausanne, CH-1066 Epalinges, Switzerland; and Laboratory of Virology, Department of Biological Sciences, Western Michigan University, Kalamazoo, MI 49008
Edited by David V. Goeddel, Tularik, Inc., South San Francisco, CA, and approved February 11, 2003 (received for review November 27, 2002)
A class of secreted poxvirus tumor necrosis factor (TNF)-binding proteins has been isolated from Tanapox-infected cell supernatants. The inhibitor bound to a TNF-affinity column and was identified as the product of the 2L gene. Sequence analysis of 2L family members from other yatapoxviruses and swinepox virus yielded no sequence homology to any known cellular gene. The expressed Tanapox virus 2L protein bound to human TNF with high affinity (Kd = 43 pM) and exhibits an unusually slow off-rate. However, 2L is unable to bind to a wide range of human TNF family members. The 2L protein can inhibit human TNF from binding to TNF receptors I and II as well as block TNF-induced cytolysis. Thus, Tanapox virus 2L represents an inhibitor of human TNF and offers a unique strategy with which to modulate TNF activity.<<
Cheers, Tuck |
