Grb3-3 cDNA and polypeptides

Abstract

The present invention relates to the Grb3-3 protein, nucleotide sequence encoding this protein, and variants thereof, such as antisense sequences. The invention further relates to vectors comprising these sequences and to methods for inducing cell death.

We claim:  
     
       1. An isolated polynucleotide selected from the group consisting of: 
       a) a polynucleotide which encodes a polypeptide comprising the uninterrupted sequence SEQ ID NO: 2, and  
       b) the complementary strand of a polynucleotide as defined in a).  
     
     
       2. The polynucleotide of  claim 1 , comprising nucleotides 37-564 of SEQ ID NO: 1 or the complementary strand of nucleotides 37-564 of SEQ ID NO: 1. 
     
     
       3. The polynucleotide of  claim 1  comprising the sequence SEQ ID NO: 1 or the complementary strand of SEQ ID NO:1. 
     
     
       4. An antisense polynucleotide comprising a polynucleotide of  claim 1 , part b, wherein said antisense polynucleotide inhibits the expression of Grb2 and Grb3-3. 
     
     
       5. An antisense polynucleotide comprising all or part of the polynucleotide of  claim 1 , part b, wherein said antisense polynucleotide specifically inhibits the expression of Grb3-3. 
     
     
       6. A vector comprising a polynucleotide according to  claim 1 . 
     
     
       7. A vector according to  claim 6 , wherein said vector is a viral vector. 
     
     
       8. A vector according to  claim 7 , selected from the group consisting of adenoviruses, retroviruses, adeno-associated viruses, herpes virus, cytomegalovirus and vaccinia virus. 
     
     
       9. A vector according to  claim 8 , wherein the virus is defective for replication. 
     
     
       10. A composition comprising a vector according to  claim 6  in a pharmaceutically acceptable carrier. 
     
     
       11. A composition comprising a polynucleotide according to  claim 1  complexed with DEAE-dextran, nuclear proteins or lipids, or incorporated into liposomes. 
     
     
       12. An isolated polypeptide having the sequence SEQ ID NO: 2. 
     
     
       13. A composition comprising a polypeptide according to  claim 12  in a pharmaceutically acceptable carrier. 
     
     
       14. An antisense polynucleotide according to  claim 5 , and comprising  wherein the polynucleotide comprises the complementary strand of the sequence joining the N-terminal SH3 domain and the residual SH2 domain of Grb3-3. 
     
     
       15. An antisense RNA comprising a sequence complementary to all or part of a polynucleotide of  claim 1 , part a, wherein said antisense RNA specifically inhibits the expression of Grb3-3. 
     
     
       16. An antisense RNA according to  claim 15 , and comprising the sequence joining the N-terminal SH3 domain and the residual SH2 domain of Grb3-3. 
     
     
       17. An antisense RNA comprising a polynucleotide of  claim 1 , part b, wherein said antisense RNA inhibits the expression of Grb2 and Grb3-3. 
     
     
       18. A process for expressing Grb 3 -   3  in a host cell, comprising introducing the vector according to    claim 6    into the host cell.    
     
     
       19. A process for expressing Grb 3 -   3  in a host cell, comprising introducing the vector according to    claim 7    into the host cell.    
     
     
       20. A process for expressing Grb 3 -   3  in a host cell, comprising introducing the vector according to    claim 8    into the host cell.    
     
     
       21. A process for expressing Grb 3 -   3  in a host cell, comprising introducing the vector according to    claim 9    into the host cell.    
     
     
       22. The process according to  claim 18 , wherein the host cell is a prokaryotic cell.  
     
     
       23. The process according to  claim 22 , wherein the prokaryotic cell is E. coli.  
     
     
       24. The process according to  claim 18 , wherein the host cell is a eukaryotic cell.  
     
     
       25. A process for preparing a Grb 3 -   3  polypeptide, comprising transforming a host cell with a vector according to    claim 6   , culturing the host cell under conditions permitting expression of the Grb 3   -   3  polypeptide, and recovering the Grb 3   -   3  polypeptide.    
     
     
       26. A process for preparing a Grb 3 -   3  polypeptide, comprising transforming a host cell with a vector according to    claim 7   , culturing the host cell under conditions permitting expression of the Grb 3   -   3  polypeptide, and recovering the Grb 3   -   3  polypeptide.    
     
     
       27. A process for preparing a Grb 3 -   3  polypeptide, comprising transforming a host cell with a vector according to    claim 8   , culturing the host cell under conditions permitting expression of the Grb 3   -   3  polypeptide, and recovering the Grb 3   -   3  polypeptide.    
     
     
       28. A process for preparing a Grb 3 -   3  polypeptide, comprising transforming a host cell with a vector according to    claim 9   , culturing the host cell under conditions permitting expression of the Grb 3   -   3  polypeptide, and recovering the Grb 3   -   3  polypeptide.    
     
     
       29. The process according to  claim 25 , wherein the host cell is a prokaryotic cell.  
     
     
       30. The process according to  claim 29 , wherein the prokaryotic cell is E. coli.  
     
     
       31. An antisense RNA according to  claim 15 , wherein the polynucleotide comprises the complementary strand of the sequence joining the N- terminal SH 3  domain and the residual SH 2  domain of Grb 3   -   3 .