Immunosuppressant target proteins

Abstract

The present invention relates to the discovery of novel proteins of mammalian origin which are immediate downstream targets for FKBP/rapamycin complexes.

1 - 50 . (Cancelled)  
     
     
         51 . A probe/primer comprising a substantially purified oligonucleotide, wherein the oligonucleotide comprises a region of nucleotide sequence which hybridizes under stringent conditions, including a wash step of 0.2×SSC at 65° C., to at least 10 consecutive nucleotides of sense or antisense sequence of SEQ ID Nos: 1 or 11.  
     
     
         52 . The probe/primer of  claim 51 , further comprising a detectable label group attached thereto.  
     
     
         53 . The probe/primer of  claim 52 , wherein said label group is selected from any of radioisotopes, fluorescent compounds, enzymes, and enzyme co-factors.  
     
     
         54 . The probe/primer of  claim 51 , wherein said probe/primer is part of a diagnostic test kit.  
     
     
         55 . The probe/primer of  claim 54 , wherein said diagnostic test kit is for any of the following: identifying transformed cells, measuring mRNA expression levels, determining whether a cell contains a mutated RAPT gene, or determining whether a RAPT gene is deleted in a cell.  
     
     
         56 . The probe/primer of  claim 51 , wherein said oligonucleotide is at least 10 nucleotides in length.  
     
     
         57 . The probe/primer of  claim 56 , wherein said oligonucleotide is at least 30 nucleotides in length.  
     
     
         58 . The probe/primer of  claim 56 , wherein said oligonucleotide is at least 50 nucleotides in length.  
     
     
         59 . The probe/primer of  claim 56 , wherein said oligonucleotide is at least 100 nucleotides in length.  
     
     
         60 . A method of identifying transformed cells using the probe/primer of  claim 54 .  
     
     
         61 . A method of measuring RAPT mRNA expression levels using the probe/primer of  claim 54 .  
     
     
         62 . A method of determining whether a cell contains a mutated RAPT gene or whether a RAPT gene is deleted in a cell using the probe/primer of  claim 51 .  
     
     
         63 . A method of screening to identify test compounds, wherein said test compounds modulate the interaction between a RAPT protein and a rapamycin/protein complex, comprising 
 (i) combining a RAPT protein, an FK506-binding protein, and a test compound; and    (ii) detecting the formation of a compound-dependent complex which includes the FK506-binding protein and the RAPT protein.    
     
     
         64 . The method of  claim 63 , wherein said method comprises screening a library of test compounds.  
     
     
         65 . The method of  claim 64 , wherein said method of screening comprises a high-throughput method of screening.  
     
     
         66 . A method of determining if a subject is at risk for a disorder characterized by unwanted cell proliferation, comprising detecting, in a tissue of the subject, the presence or absence of a genetic lesion characterized by 
 (i) a mutation of a gene encoding a RAPT protein, or a homolog thereof;    (ii) the mis-expression of a gene encoding a RAPT protein, or a homolog thereof; or    (iii) the mis-expression of a RAPT protein, or a homolog thereof.    
     
     
         67 . The method of  claim 66 , wherein detecting the genetic lesion comprises detecting at least one of 
 (i) a deletion of one or more nucleotides from the RAPT gene;    (ii) an addition of one or more nucleotides to the RAPT gene;    (iii) a substitution of one or more nucleotides of the RAPT gene;    (iv) a gross chromosomal rearrangement of the RAPT gene;    (v) an alteration in the level of a messenger RNA transcript of the RAPT gene;    (vi) the presence of a non-wild type splicing pattern of a messenger RNA transcript of the RAPT gene; or    (vii) a non-wild type level of the protein.    
     
     
         68 . The method of  claim 66  or 67, wherein detecting the genetic lesion comprises 
 (i) providing a probe/primer including an oligonucleotide comprising a region of nucleotide sequence which hybridizes under stringent conditions, including a wash step of 0.2×SSC at 65 ° C., to at least 10 consecutive nucleotides of sense or antisense sequence of SEQ ID Nos: 1, 11, or 5′ or 3′ flanking sequences naturally associated with the RAPT gene;    (ii) exposing the probe/primer to the tissue; and    (iii) detecting, by hybridization of the probe/primer to the nucleic acid, the presence or absence of the genetic lesion.