Novel notch-origin polypeptides and biomarkers and reagents using the same

Abstract

It is intended to provide extracellular markers whereby Notch signal transduction can be detected. Polypeptides (Nβ), which are novel peptides originating in Notch protein and released form cells in the step of the nuclear migration of NICH (Notch intracellular cytoplasmic domain) due to the extracellular digestion and the subsequent protein digestion in the membrane during a series of the Notch protein digestion, are referred to as markers. These peptides (Nβ) are released from the cells in proportion to the Notch signal depending on presenilin. By detecting these peptides, the Notch signal transduction, cell differentiation, cell tumorigenesis, apoptosis, Alzheimer's disease, etc. can be monitored.

1 - 21 . (canceled) 
     
     
         22 . A method for detecting a condition that exhibits abnormal Notch signal transduction, the method comprising the steps of:
 detecting a level of a polypeptide having an amino acid sequence selected from a group consisting of SEQ ID NOS: 10 to 18 expressed in a sample obtained from an object;   comparing the level detected in the detecting step with a level of a corresponding polypeptide detected from a normal object; and   identifying abnormality of a Notch signal transduction when the level of the polypeptide in the sample obtained from the object is either significantly higher or lower than the level of the corresponding polypeptide of the normal object.   
     
     
         23 . The method for detecting a condition that exhibits abnormal Notch signal transduction according  claim 22 ,
 wherein the detecting step of the level of the polypeptide is conducted by using a reagent comprising an antibody that recognizes the polypeptide.   
     
     
         24 . The method for detecting a condition that exhibits abnormal Notch signal transduction according  claim 23 , wherein the antibody is at least one selected from the group consisting of a monoclonal antibody and a polyclonal antibody. 
     
     
         25 . The method for detecting a condition that exhibits abnormal Notch signal transduction according  claim 23 ,
 wherein the reagent further comprises a labeled antibody that recognizes the polypeptide or a labeled antibody that recognizes as an antigen said antibody that recognizes the polypeptide.   
     
     
         26 . The method for detecting a condition that exhibits abnormal Notch signal transduction according  claim 25 , wherein the labeled antibody is labeled by using a fluorescent substance, an enzyme, or a radioactive substance. 
     
     
         27 . The method for detecting a condition that exhibits abnormal Notch signal transduction according  claim 22 , wherein the method detects a functional disorder of presenilin. 
     
     
         28 . The method for detecting a condition that exhibits abnormal Notch signal transduction according  claim 27 , wherein the functional disorder of presenilin is at least one selected from the group consisting of abnormal cell differentiation, tumor, apoptosis, and Alzheimer's disease. 
     
     
         29 . The method for detecting a condition that exhibits abnormal Notch signal transduction according  claim 22 , wherein the object is a mammal.