Interleukin-1beta converting enzyme like cysteine protease

Abstract

A new member of a family of ICE-like cysteine proteases has been identified. The protease family is termed LICE (Like ICE) and the family member described herein is LICE3. LICE3 polypeptides, nucleic acids encoding LICE3 and vectors and host cells for the expression LICE3 are disclosed. Also disclosed are methods for identifying LICE3 agonists and antagonists, and methods for treatment of disorders characterized by altered apoptosis.

What is claimed is:  
     
         1 . An isolated nucleic acid encoding a polypeptide comprising at least one of the biological activities of LICE3 wherein the nucleic acid is selected from the group consisting of: 
 a) the nucleic acid shown in FIG. 1 (SEQ ID NO: ______);    b) nucleic acids which hybridize to the polypeptide coding regions of the nucleic acids shown in FIG. 1 (SEQ ID NO: ______) and remain hybridized to the nucleic acids under high stringency conditions; and    c) nucleic acids which are degenerate to the nucleic acids of (a) or (b).    
     
     
         2 . The nucleic acid of  claim 1  which is cDNA, genomic DNA, synthetic DNA or RNA.  
     
     
         3 . A polypeptide encoded by the nucleic acid of  claim 1 .  
     
     
         4 . The nucleic acid of  claim 1  including one or more codons preferred for  Escherichia coli  expression.  
     
     
         5 . The nucleic acid of  claim 1  having a detectable label attached thereto.  
     
     
         6 . The nucleic acid of  claim 1  comprising the polypeptide-coding region of FIG. 1 (SEQ ID NO:______).  
     
     
         7 . A nucleic acid encoding a polypeptide having the amino acid sequence of SEQ. ID. NO.______.  
     
     
         8 . An expression vector comprising the nucleic acid of  claim 1 .  
     
     
         9 . The expression vector of  claim 8  wherein the nucleic acid comprises the polypeptide-encoding region as shown in FIG. 1 (SEQ ID NO:______).  
     
     
         10 . A host cell transformed or transfected with the expression vector of  claim 8 .  
     
     
         11 . The host cell of  claim 10  which is a eucaryotic or procaryotic cell.  
     
     
         12 . The host cell of  claim 11  which is  Escherichia coli.    
     
     
         13 . A process for the production of LICE3 polypeptide comprising: 
 growing under suitable nutrient conditions host cells transformed or transfected with the nucleic acid of  claim 1;  and    isolating the polypeptide product of the expression of the nucleic acid.    
     
     
         14 . A polypeptide produced by the process of  claim 13 .  
     
     
         15 . A polypeptide having the amino acid sequence as shown in FIG. 1 (SEQ ID NO:______) or a derivative thereof having at least about 60% homology to the amino acid sequence as shown in FIG. 1 (SEQ ID NO: ______) wherein the polypeptide has at least one of the biological activities of LICE3.  
     
     
         16 . An antibody or fragment thereof which specifically binds LICE3.  
     
     
         17 . The antibody of  claim 16  which is a monoclonal antibody.  
     
     
         18 . A method for detecting the presence of LICE3 in a biological sample comprising: 
 incubating the sample with the antibody of  claim 16  under conditions that allow binding of the antiboby to LICE3; and    detecting the bound antibody.    
     
     
         19 . A method to assess the ability of a candidate compound to bind LICE3 comprising: 
 incubating LICE3 with the candidate compound under conditions that allow binding; and    measuring the bound compound.    
     
     
         20 . The method of  claim 19  wherein the compound is an antagonist of LICE3.  
     
     
         21 . A method of regulating expression of LICE3 in an animal comprising administering to the animal a nucleic acid complementary to the nucleic acids as shown in FIG. 1 (SEQ ID NO:______).  
     
     
         22 . A pharmaceutical composition comprising a therapeutically effective amount of LICE3 in a pharmaceutically acceptable carrier, adjuvant, solubilizer, stabilizer and/or anti-oxidant.  
     
     
         23 . The composition of  claim 22  wherein LICE3 is human LICE3.  
     
     
         24 . A method of treating a disorder characterized by increased apoptosis comprising administering a therapeutically effective amount of a LICE3 antagonist.  
     
     
         25 . The method of  claim 24  wherein the disorder is a viral infection, an autoimmune disease, or a nervous system degeneration.  
     
     
         26 . A method of treating a disorder characterized by increased cell proliferation comprising administering a therapeutically effective amount of LICE3.  
     
     
         27 . The method of  claim 26  wherein the disorder is cancer.