Centrosome proteins and uses thereof

Abstract

The invention includes nucleic acids and polypeptides that play important roles in centrosomes and cellular functions involving centrosomes. In addition, the invention encompasses antibodies, ribozymes, antisense nucleic acids, RNAis, and siRNAs that can be used to modulate the function of the nucleic acids and polypeptides of the invention. Such modulation can be useful in detecting, diagnosing, and treating abnormal centrosome function.

1 . An isolated polypeptide encoded by a nucleic acid comprising SEQ ID NO:1.  
     
     
         2 . The isolated polypeptide of  claim 1 , encoded by a nucleic acid consisting of SEQ ID NO:1.  
     
     
         3 . An isolated polypeptide comprising a sequence that is at least 95% identical to the full length of SEQ ID NO:2.  
     
     
         4 . An isolated polypeptide comprising SEQ ID NO:2, wherein 10% or fewer of the amino acids are replaced by conservative amino acid substitutions.  
     
     
         5 . The isolated polypeptide of  claim 3 , wherein the polypeptide comprises SEQ ID NO:2.  
     
     
         6 . The isolated polypeptide of  claim 3 , wherein the polypeptide consists of SEQ ID NO:2.  
     
     
         7 . An isolated antibody that binds to a polypeptide consisting of SEQ ID NO:2.  
     
     
         8 . A method of reducing cell division, the method comprising administering to a cell an amount of a centriolin modulator effective to disrupting microtubule organization in the cell, wherein the modulator is selected from the group consisting of an antisense oligonucleotide targeting centriolin, a small interfering RNA (siRNA) targeting centriolin, a morpholino oligonucleotide targeting centriolin, a ribozyme targeting centriolin, and an anti-centriolin antibody, thereby reducing cell division.  
     
     
         9 . The method of  claim 8 , wherein the centriolin modulator is a centriolin siRNA.  
     
     
         10 . The method of  claim 9 , wherein the centriolin siRNA comprises SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, or SEQ ID NO:15.  
     
     
         11 . The method of  claim 8 , wherein the centriolin modulator is a centriolin antisense nucleic acid.  
     
     
         12 . The method of  claim 8 , wherein the centriolin modulator is a centriolin ribozyme.  
     
     
         13 . The method of  claim 8 , wherein the centriolin modulator is an anti-centriolin antibody.  
     
     
         14 . The method of  claim 13 , wherein the antibody is produced in vivo.  
     
     
         15 . The method of  claim 13 , wherein the antibody is produced in vitro.  
     
     
         16 . The method of  claim 8 , wherein cell division is reduced to treat cancer, leukemia, psoriasis, Hodgkin's disease, lymphoma, myelofibrosis, polycythemia vera, or another cell proliferative disorder.  
     
     
         17 . A method of reducing cell division, the method comprising administering to a cell an amount of a pericentrin-B modulator effective to disrupt microtubule organization in the cell, wherein the modulator is selected from the group consisting of an antisense oligonucleotide targeting pericentrin-B, a small interfering RNA (siRNA) targeting pericentrin-B, a morpholino oligonucleotide targeting pericentrin-B, a ribozyme targeting pericentrin-B, and an anti- pericentrin-B antibody, thereby reducing cell division.  
     
     
         18 . The method of  claim 17 , wherein the pericentrin-B modulator is an siRNA.  
     
     
         19 . The method of  claim 18 , wherein the siRNAis SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, or SEQ ID NO:23.  
     
     
         20 . The method of  claim 17 , wherein the pericentrin-B modulator is an antisense nucleic acid targeting pericentrin-B.  
     
     
         21 . The method of  claim 17 , wherein the pericentrin-B modulator is a ribozyme targeting pericentrin-B.  
     
     
         22 . The method of  claim 17 , wherein the pericentrin-B modulator is an anti-pericentrin-B antibody.  
     
     
         23 . The method of  claim 22 , wherein the antibody is produced in vivo.  
     
     
         24 . The method of  claim 22 , wherein the antibody is produced in vitro.  
     
     
         25 . The method of  claim 17 , wherein cell division is reduced to treat cancer, leukemia, psoriasis, Hodgkin's disease, lymphoma, myelofibrosis, polycythemia vera, or another cell proliferative disorder.  
     
     
         26 . A method of treating abnormal centrosome function in a cell, the method comprising administering to the cell an amount of centriolin effective to restore nonmal centrosome fuinction, wherein normal centrosome function is restored.  
     
     
         27 . A method of treating abnormal centrosome function in a cell, the method comprising administering to the cell an amount of pericentrin-B effective to restore normal centrosome function, wherein normal centrosome fuinction is restored.