>>SOUTH SAN FRANCISCO, Calif., April 15 /PRNewswire-FirstCall/ -- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL - News) today announced that two presentations related to its cancer research will be made at the 96th Annual Meeting of the American Association for Cancer Research (AACR), taking place April 16-20 in Anaheim, California.
Details are as follows:
Presentation Time: Monday, April 18, 8:00 am - 12:00 pm
Presentation Number: 2019
Title: Requirement for the tyrosine kinase Axl in angiogenesis and
tumor growth
Presentation Time: Wednesday, April 20, 8:00 a.m. - 12:00 p.m.
Presentation Number: 5469
Title: Critical role of the ubiquitin Ligase activity of Np95, a nuclear
RING finger protein, in tumor cell growth
Rigel is investigating both the kinase system and the ubiquitin ligase system for the discovery of potential novel cancer therapeutics. Rigel has discovered potent and highly selective small molecule inhibitors of selected kinases and ubiquitin ligases. Some of these inhibitors have shown positive activity in animal models of cancer and are in preclinical development at Rigel. Rigel has collaborations with Merck, Inc. and Daiichi Pharmaceuticals on selected ligase targets in cancer.
About Ubiquitin Ligases
Ubiquitin ligases are enzymes that regulate protein degradation within the cell. The breakdown of proteins, in turn, affects many important cellular functions, including cell division. Targeting ligases represents a novel approach to treating diseases where normal cellular processes are out of balance. Because unchecked cell division is the hallmark of cancer, researchers believe that this part of the cell machinery represents a particularly compelling target for cancer therapies. Ubiquitin ligase targets are numerous and modular. This provides the potential for intervening in a highly specific fashion in a disease, potentially improving efficacy and minimizing side effects.
About Rigel (www.rigel.com) <<
snip
Edit: here's a year old full text freebie on Np95:
"Np95 Is a Histone-Binding Protein Endowed with Ubiquitin Ligase Activity"
mcb.asm.org
Unclear to me, based on previous publications why this would be a good target (how specific to tumor growth), so the Rigel presentation should be interesting.
Next Edit:
>>Abstract Number: 5469
Presentation Title: Critical role of the ubiquitin ligase activity of Np95, a nuclear RING finger protein, in tumor cell growth
Presentation Start/End Time: Wednesday, Apr 20, 2005, 8:00 AM -12:00 PM
Board Number: Board #4
Author Block: Yonchu Jenkins, Vadim Markovtsov, Wayne Lang, Poonam Sharma, Denise Pearsall, Justin Warner, Christian Franci, Betty Huang, Jianing Huang, George C. Yam, Joseph P. Vistan, Erlina Pali, Jorge Vialard, Michel Janicot, James B. Lorens, Donald G. Payan, Yasumichi Hitoshi. Rigel, Inc., S. San Francisco, CA, Johnson and Johnson Pharmaceutical Research Division, Beerse, Belgium, University of Bergen School of Medicine, Bergen, Norway
Early cellular events associated with tumorigenesis often include loss of cell cycle checkpoints or alteration in growth signaling pathways. Identification of novel genes involved in cellular proliferation may lead to new classes of therapeutics for cancer treatment. By screening a tetracycline-inducible cDNA library in A549 cells for genes that interfere with cell cycle progression, we have identified a fragment of Np95, a nuclear RING finger protein, that serves as a dominant negative effecter of cell growth. Reduction of Np95 message levels using an Np95-specific siRNA led to decreased growth rates in several tumor cell lines. In addition, activation of a number of different cell cycle checkpoints resulted in downregulation of Np95. The primary sequence of Np95 contains a PHD and a RING finger domain, both of which are structural hallmarks of ubiquitin E3 ligases which facilitate the transfer of ubiquitin from a donor E2 molecule to a substrate. Post-translation modification of proteins by ubiquitin affects a range of cellular processes such as protein degradation, transcriptional regulation, and intracellular trafficking. We have confirmed using an in vitro autoubiquitination assay that Np95 displays RING finger dependent E3 ligase activity. Overexpression of a GFP-fused Np95 RING finger mutant that lacks ligase activity sensitizes cells to treatment with various chemotherapeutics, implicating the RING domain of Np95 as a functional determinant of growth regulation. Taken together, our results suggest a general requirement for Np95 in tumor cell proliferation. <<
Cheers, Tuck |
