Interleukin-1 Beta Converting Enzyme Like Apoptosis Protease-3 and 4

Abstract

Disclosed are human interleukin-1 β converting enzyme like apoptosis proteases-3 and 4 and DNA (RNA) encoding such polypeptides. Also provided is a procedure for producing such polypeptides by recombinant techniques and antibodies and antagonists against such polypeptides. Also provided are methods of using the polypeptides, for example, as an antitumor agent, and antiviral agent, and antibodies and antagonists against such polypeptides for example, for treating Alzheimer's disease, Parkinson's disease, rheumatoid arthritis and head injury. Diagnostic assays for identifying mutations in nucleic acid sequence encoding a polypeptide of the present invention and for detecting altered levels of the polypeptide of the present invention for detecting diseases are also disclosed.

1 . An isolated polynucleotide comprising a member selected from the group consisting of:
 (a) a polynucleotide encoding the polypeptide comprising amino acid 1 to amino acid 341 as set forth in SEQ ID NO:2;   (b) a polynucleotide encoding the polypeptide comprising amino acid 1 to amino acid 277 as set forth in SEQ ID NO:4;   (c) a polynucleotide capable of hybridizing to and which is at least 95% identical to the polynucleotide of (a) or (b); and   (d) a polynucleotide fragment of the polynucleotide of (a), (b) or (c).   
     
     
         2 . The polynucleotide of  claim 1  wherein the polynucleotide is DNA. 
     
     
         3 . The polynucleotide of  claim 1  wherein the polynucleotide is RNA. 
     
     
         4 . The polynucleotide of  claim 1  wherein the polynucleotide is genomic DNA. 
     
     
         5 . An isolated polynucleotide comprising a member selected from the group consisting of:
 (a) a polynucleotide which encodes a mature polypeptide having the amino acid sequence expressed by the DNA contained in ATCC™ Deposit No. 75875;   (b) a polynucleotide which encodes a mature polypeptide having the amino acid sequence expressed by the DNA contained in ATCC™ Deposit No. 75873;   (c) a polynucleotide capable of hybridizing to and which is at least 95% identical to the polynucleotide of (a); and   (d) a polynucleotide fragment of the polynucleotide of (a), (b) or (c).   
     
     
         6 . A vector containing the DNA of  claim 2 . 
     
     
         7 . A host cell genetically engineered with the vector of  claim 6 . 
     
     
         8 . A process for producing a polypeptide comprising: expressing from the host cell of  claim 7  the polypeptide encoded by said DNA. 
     
     
         9 . A process for producing cells capable of expressing a polypeptide comprising genetically engineering cells with the vector of  claim 6 . 
     
     
         10 . A polypeptide selected from the group consisting of (i) a polypeptide having the deduced amino acid sequence of SEQ ID NO:2 and fragments, analogs and derivatives thereof; (ii) a polypeptide encoded by the cDNA of ATCC™ Deposit No. 75875 and fragments, analogs and derivatives of said polypeptide; (iii) a polypeptide having the deduced amino acid sequence of SEQ ID NO:4 and fragments, analogs and derivatives thereof; and (iv) a polypeptide encoded by the cDNA of ATCC™ Deposit No. 75873 and fragments, analogs and derivatives of said polypeptide. 
     
     
         11 . A compound which inhibits activation of the polypeptide of  claim 10 . 
     
     
         12 . A method for the treatment of a patient having need of ICE-LAP-3 comprising:
 administering to the patient a therapeutically effective amount of the polypeptide of  claim 10 .   
     
     
         13 . The method of  claim 12  wherein said therapeutically effective amount of the polypeptide is administered by providing to the patient DNA encoding said polypeptide and expressing said polypeptide in vivo. 
     
     
         14 . A method for the treatment of a patient having need of ICE-LAP-4 comprising:
 administering to the patient a therapeutically effective amount of the polypeptide of  claim 10 .   
     
     
         15 . The method of  claim 14  wherein said therapeutically effective amount of the polypeptide is administered by providing to the patient DNA encoding said polypeptide and expressing said polypeptide in vivo. 
     
     
         16 . A method for the treatment of a patient having need to inhibit an ICE-LAP 3 polypeptide comprising: administering to the patient a therapeutically effective amount of the compound of  claim 11 . 
     
     
         17 . A method for the treatment of a patient having need to inhibit an ICE-LAP 4 polypeptide comprising: administering to the patient a therapeutically effective amount of the compound of  claim 11 . 
     
     
         18 . A process for diagnosing a disease or a susceptibility to a disease related to an under-expression of the polypeptide of  claim 10  comprising:
 determining a mutation in a nucleic acid sequence encoding said polypeptide.   
     
     
         19 . A diagnostic process comprising:
 analyzing for the presence of the polypeptide of  claim 10  in a sample derived from a host.   
     
     
         20 . A method for identifying compounds which inhibit the polypeptide of  claim 10  comprising:
 contacting the polypeptide with its natural substrate and a compound under conditions where the substrate is normally cleaved by the polypeptide; and   determining whether the compound inhibits the polypeptide by detecting the absence of cleaved substrate.