Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
1999-01-20
2003-01-21
Huff, Sheela (Department: 1642)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C536S001001, C536S018700, C536S022100, C536S023100, C536S023400, C435S320100, C435S325000, C435S041000, C435S069100, C530S350000
Reexamination Certificate
active
06509457
ABSTRACT:
This invention was made in the course of research sponsored by the National Institutes of Health. The U. S. Government may have certain rights in this invention.
This invention relates to newly identified polynucleotides and polypeptides, and their production and uses, as well as their variants, agonists and antagonists, and their uses. In particular, the invention relates to polynucleotides and polypeptides of the AAC-11 (antiapoptosis clone-11) family, hereinafter referred to as “AAC-11”.
Programmed cell death, or apoptosis, plays a critical role in development, tissue renewal and repair, and tumor growth (Thompson. C.B.
Science
1995, 267:1456-1462; Stewart, B. W.
J. Natl. Cancer Inst
. 1994, 86:1286-1296). Apoptosis may be induced directly by a host of physiological or nonphysiological signals including tumor necrosis factor, FAS ligand, oxidative stress, and viruses. Alternatively, apoptosis occurs after removal of extracellular growth factors, cytokines, or attachment substrata or by the inappropriate expression of cell cycle components. The latter observations suggest that apoptosis in proliferating cells reflects a conflict in the cell cycle or a default pathway in cell cycle progression that is diverted by specific intracellular factors (Evan et al.
Curr. Opin. Cell Biol
. 1995, 7:825-834; Meikrantz, W. and R. Schlegel
J. Cell. Biochem
. 1995, 58:160-174). Viewed differently, cellular viability is dependent on the functional balance of factors that favor apoptosis versus extracellular (e.g., growth factors) and intracellular survival signals. Examples of such survival factors include bcl-2 and related family members (Yang, E. and S. J. Korsmeyer
Blood
1996, 88:386-401), proteins that inhibit tumor necrosis factor killing such as MnSOD (Wong et al.
Cell
1989, 58:923-931), A20 (Opipari et al.
J. Biol. Chem
. 1992, 267:12424-12427), and plasminogen activator inhibitor 2 (Kroemer et al.
FASEB J
. 1995, 9:1277-1287; Dickinson et al.
J. Biol. Chem
. 1995. 270:27894-27904), as well as recently identified proteins such as calcium-binding protein ALG-2 (Vito et al.
Science
1996, 271:521-525) and mammalian homologues of baculovirus IAP gene (Liston et al.
Nature
1996, 379:349-353; Hay et al.
Cell
1995, 83: 1253-1262; Duckett et al.
EMBO J
. 1996, 15:2685-2694).
Many growth factors and cytokines act as cellular survival factors by preventing apoptosis. However, the specific genes and corresponding proteins that mediate cell survival are poorly defined. For example insulin-like growth factor I (IGF-I) prevents apoptosis in diverse settings, including deprivation of growth factors and cytokines (Barres et al.
Cell
1992, 70:31-46; Rodriguez-Tarduchy et al.
J. Immunol
. 1992, 149:535-540), cell cycle dysregulation (Harrington et al.
EMBO J
. 1994, 13:3286-3295; Sell et al.
Cancer Res
. 1995, 55:303-306), ischemia (Buerke et al.
Proc. Natl. Acad. Sci. USA
1995, 92:8031-8035), administration of tumor necrosis factor, hyperosmotic shock (Matthews. C. C. and Feldman. E. L.
J. Cell Physiol
. 1996, 166:323-331), and activation of IL-lb-converting enzyme (Yong-Kuen et al.
J. Biol. Chem
. 1996, 271:5112-5117). However, the mechanism by which the activated IGF-I receptor inhibits apoptosis is unknown. For growth factor-regulated cells such as murine fibroblasts, long-term survival in the presence of IGF-I does require continuous gene expression (Tamm, I. and Kikuchi, T. J.
Cell. Physiol
. 1990, 143:494-500). IGF-I modulates gene expression both transcriptionally and for survival by stabilizing existing mRNA transcripts (Zumstein, P. and Stiles C. D.
J. Biol. Chem
. 1987 262:11252-11260).
In a more recent publication by Ambrosini et al., a new anti-apoptosis gene referred to as “survivin” is disclosed (Ambrosini, G. et al.
Nat. Med
. 1997. 3:917-921). This gene encodes a 16.5 kDa protein and is found in more than 50% of non-Hodgkin's lymphomas examined. The mRNA detected was 1.9 kb.
A novel cDNA has now been isolated and is referred to herein as antiapoptosis clone 11 (AAC-11). This clone expresses a 25 kDa protein that prevents apoptosis caused by deprivation of growth factors in a cell.
SUMMARY OF THE INVENTION
The present invention relates to AAC-11 in particular AAC-11 polypeptides and AAC-11 polynucleotides, recombinant materials and methods for their production. In another aspect, the present invention relates to methods for using such polypeptides and polynucleotides, including methods of inhibiting apoptosis in a cell. In a further aspect, the present invention relates to identifying agonists and antagonists using the materials provided by the invention. In still a further aspect, the present invention relates to compositions and methods for inhibiting apoptosis in a cell, preferably an animal cell, most preferably a human cell. In another aspect, the present invention relates to a method of inhibiting apoptosis in a cell, preferably an animal cell, most preferably a human cell, wherein an effective amount of a protein encoded by a AAC-11 polynucleotide so that apoptosis in the cell is inhibited. In another aspect, the present invention relates to a method of inhibiting apoptosis in a cell, preferably an animal cell, most preferably a human cell, wherein an effective amount of a AAC-11 polynucleotide is administered to the cell so that the cell encodes the polynucleotide thereby inhibiting apoptosis in the cell. In yet a further aspect, the present invention relates to compositions and methods for inducing apoptosis in a cell by inhibiting expression of the AAC-11 polynucleotides or the activity of the AAC-11 polypeptides encoded thereby.
REFERENCES:
Tewari et al. AAC-11, a Novel cDNA that inhibits apoptosis after Growth Factor Withdrawal. Cancer Research 57:4063-4069, 1997.*
Amino acid databases, Accession Nos. O15441, O35841, U35846 and U83857, 1997 & 1998.*
Nucleic acid databases, Accession Nos. O15441, O35841, U35846, U83857, 1997 & 1998.
Rubin Raphael
Tewari Manorama
Dechert
Deibert Thomas S.
Harris Alana M.
Huff Sheela
Thomas Jefferson University
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