Cancer Treatment and Immune System Regulation Through FAT10 Pathway Inhibition

Abstract

Described herein are methods of inhibiting mitosis, treating cancer and/or treating immune disorders through the use of agents that inhibit FAT10 and/or the FAT10 pathway.

1 - 54 . (canceled) 
     
     
         55 . A method of treating an immune disorder in a subject comprising administering to the subject an agent that inhibits the FAT10 pathway 
     
     
         56 . The method of  claim 55 , wherein the immune disorder comprises an autoimmune disorder, an inflammatory disease or an allergy. 
     
     
         57 . The method of  claim 56 , wherein the immune disorder is an autoimmune disease selected from Lupus, Scleroderma, hemolytic anemia, vasculitis, Grave's disease, rheumatoid arthritis, multiple sclerosis, Goodpasture's syndrome, pernicious anemia and/or myopathy. 
     
     
         58 . The method of  claim 56 , wherein the immune disorder is an inflammatory disease selected from acne vulgaris, asthma, celiac disease, chronic prostatitis, glomerulonephritis, inflammatory bowel disease, pelvic inflammatory disease, reprofusion injury, rheumatoid arthritis, sarcoidosis, transplant rejection, vasculitis and/or interstial cystitis. 
     
     
         59 . The method of  claim 56 , wherein the immune disorder comprises an allergy selected from food allergies, drug allergies and/or environmental allergies. 
     
     
         60 . The method of  claim 56 , wherein the immune disorder comprises asthma, inflammatory bowel disease, Crohn's disease or colitis. 
     
     
         61 . The method of  claim 55 , wherein the agent inhibits the FAT10 pathway by inhibiting the activity or expression of FAT10. 
     
     
         62 . The method of  claim 55 , wherein the agent inhibits the formation of a conjugate between FAT10 and a FAT10 substrate 
     
     
         63 . The method of  claim 55 , wherein the agent is a small molecule, a polypeptide or inhibitory nucleic acid. 
     
     
         64 . The method of  claim 63 , wherein the agent is an inhibitory nucleic acid specific for an mRNA that encodes FAT10. 
     
     
         65 . The method of  claim 63 , wherein the inhibitory nucleic acid is selected from the group consisting of siRNA, shRNA, and an antisense RNA molecule, or a nucleic acid that encodes a molecule selected from the group consisting of siRNA, shRNA, and/or an antisense RNA molecule. 
     
     
         66 . The method of  claim 65 , wherein the inhibitory nucleic acid is an siRNA, an shRNA or an antisense RNA molecule. 
     
     
         67 . The method of  claim 61 , wherein the inhibitory nucleic acid is a nucleic acid that encodes an siRNA, an shRNA or an antisense RNA molecule. 
     
     
         68 . A method of determining whether a test agent is a candidate therapeutic agent for the treatment of an immune disorder comprising: a) forming a test reaction mixture comprising a FAT10 protein, a FAT10 substrate, a concentrated mammalian cell extract and a test agent; b) incubating the test reaction under conditions conducive for the formation of a conjugate between the FAT10 protein and the FAT10 substrate; and c) determining the amount of the conjugate in the test reaction mixture; wherein a test agent that reduces the amount of the conjugate in the test reaction mixture compared to the amount of the conjugate in a control reaction mixture is a candidate therapeutic agent for the treatment of an immune disorder. 
     
     
         69 . The method of  claim 68 , wherein the FAT10 substrate is a protein encoded by a nucleic acid of SEQ ID NO: 3-465. 
     
     
         70 . The method of  claim 68 , wherein the control reaction mixture is substantially identical to the test reaction mixture except that the control reaction mixture does not comprise a test agent. 
     
     
         71 . The method of  claim 68 , wherein the control reaction mixture is substantially identical to the test reaction mixture except that the control reaction mixture comprises a placebo agent instead of a test agent. 
     
     
         72 . The method of  claim 68 , wherein the FAT10 protein is linked to a detectable moiety. 
     
     
         73 . The method of  claim 72 , wherein the FAT10 substrate is anchored to a solid support. 
     
     
         74 . The method of  claim 68 , further comprising the step of isolating the conjugate from unconjugated FAT10 protein. 
     
     
         75 . The method of  claim 68 , wherein the FAT10 substrate is linked to a detectable moiety. 
     
     
         76 . The method of  claim 75 , wherein the FAT10 protein is anchored to a solid support. 
     
     
         77 . The method of  claim 68 , further comprising the step of isolating the conjugate from unconjugated FAT10 substrate. 
     
     
         78 . A method of determining whether a test agent is a candidate therapeutic agent for the treatment of an immune disorder comprising: a) contacting a cell, a tissue sample or a cell extract with the test agent; and b) detecting the expression or activity of FAT10 in the cell, tissue sample or cell extract; wherein a test agent that decreases the expression or activity of FAT10 is a candidate therapeutic agent for the treatment of an immune disorder. 
     
     
         79 . The method of  claim 78 , wherein the expression of FAT10 is detected by detecting FAT10 mRNA level or FAT10 protein level in the cell. 
     
     
         80 . The method of  claim 78 , wherein the activity of FAT10 is detected in the cell or cell extract by detecting a conjugate comprising FAT10 and a FAT10 substrate.