Effector Targets

Clearly we have achieved a wealth of understanding of the multitude DNA repair and cell cycle damage response pathways. It is also clear that alterations in these pathways contribute to cancer, aging, and various other human disease states. Now that we have made such incredible advances in understanding the genetic and biochemical details of these pathways, it will be the ultimate challenge to apply this understanding to devise better ways to ameliorate or even cure the many human disease states that they impact. 

Gillet, L. C. J., and Scharer, O. D. Molecular mechanisms of mammalian global genome nucleotide excision repair. Chem. Rev. 106, 253-276, 2006. 

Huffman, J. L., Sundheim, O., and Tainer, J. A. DNA base damage recognition and removal new twists and grooves. Mutat. Res. 577, 55-76, 2005. 

Kadyrov, F. A., Dzantiev, L., Constantin, N., and Modrich, P. Endonucleolytic function of MutLalpha in human mismatch repair. Cell 126, 297-308, 2006. 

Ljungmna, M. (Ed.). Mechanisms of DNA repair special issue dedicated to Philip Hanawalt, Mutat. Res. 577, 2005. 

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Polakis, P, McCormick, E Structural requirements for the interaction of p21 with GAP, exchange factors, and its biological effector target. /. Biol. Chem. 268 9157-9160, 1993. 

NO mediates its effects by covalent modification of proteins. There are three major effector targets of NO (Figure 19-1) Metalloproteins... 

Effector targets of IL-3 are (1) the pluripotential hematopoietic stem cells and progenitor cells and (2) the other several mature cells, such as B lymphocytes, macrophages, basophils, eosinophils, mast cells, and keratinocytes. ... 

HOMEOSTATIC COMPONENTS SENSOR CONTROL CENTER EFFECTOR TARGET... 

Yersinia effectors target mammalian signalling pathways, S. J. Juris, F. Shao and J. E. Dixon, Cell. Microbiol., 2002, 4, 201. 

Fig. (3). QS-21 dose response curve for induction of MHC Class 1-restricted cytotoxic T lymphocyte response. C57BL/6 mice (10 per saponin adjuvant dose) were immunized with OVA and different doses of QS-21 by subcutaneous administration at days 0, 14, and 28. After the third immunization, splenocytes were harvested and stimulated in vitro with OVA for use as effector cells in a CTL assay. Target cells were E.G7-OVA [Effector Target ratio 25 1 ( ), 12 1 ( ), and 6 1 ( )], and EL4 cells [Effector Target ratio 25 1 (O)]. E.G7-OVA are EL4 cells transfected with the OVA gene. Adapted from Newman et al J. Immunol., 1992, 148, 2357-2362, copyright 1992, with permission from The American association of immunologists.

Toxicoiogy LD50 (oral, rat) 1484 mg/kg, (IP, rat) 138 mg/kg toxic poison by IP and parenteral routes mod. toxic by ing. irritant mutagen experimental reproductive effector target organs nerves, lungs TSCA listed Hazardous Decomp. Prods. Heated to decomp., emits toxic fumes of CF... 

Toxicology LD50 (oral, rat) 3600 mg/kg, (IP, rat) 634 mg/kg, (subcut., mouse) 1625 mg/kg harmful by inh., ing., skin contact may cause irritation absorp. into body causes methemoglobinemia which may cause cyanosis onset may be delayed may cause convulsions, ataxia, coma, cardiac effects, respiratory depression, etc. mutagen possible carcinogen reproductive effector target organs blood, kidneys, liver TSCA listed... 

Toxicology LDLo (oral, mouse) 3 g/kg, (subcut, mouse) 900 mg/kg, (IV, mouse) 1000 mg/kg poison by IV route mod. toxic by ing, subcut, routes highly toxic by in],—destroys red blood cells severe irritant possible sensitizer sternutator experimental reproductive effector target organs blood, Gl system, nerves, liver Environmental Toxic to fish Precaution Wear splash goggles and lab coat... 

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