BAG3 nucleotide and protein sequences to be used in research, diagnostics and therapy for cell death-involving diseases, and for modulation of cell survival and/or death

Abstract

The present invention provides BAG3 nucleotide and protein sequences to be used in research, diagnostics and therapy for modulation of cell survival and/or death, in particular in leukemias, other neoplasias and apoptosis-involving diseases. More particularly the invention refers to the use of specific antisense-based constructs and peptide-specific polyclonal and monoclonal antibodies in leukemias, other neoplasias and cell death-involving diseases.

1 .- 29 . (canceled) 
     
     
         30 . A method for modulating apoptosis in a cell by regulating BAG-3 expression, which comprises using isolated polynucleotides or oligonucleotides that recognize or modulate BAG3 protein expression and wherein said polynucleotides or oligonucleotides are selected from the group of nucleic acid sequences consisting of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, and fragments and a complementary sequence thereof. 
     
     
         31 . The method according to  claim 30 , wherein said isolated polynucleotides or oligonucleotides have at least 90% homology to BAG3 SEQ ID NO:1 or fragments or a complementary sequence thereof. 
     
     
         32 . The method according to  claim 30 , wherein said cell is a primary cell. 
     
     
         33 . The method according to  claim 30 , wherein said polynucleotides or oligonucleotides consist of SEQ ID NO:9, SEQ ID NO:10 or SEQ ID NO:11 or a sequence encoding a peptide of SEQ ID NO:15, SEQ ID NO:6, SEQ ID NO:17 or SEQ ID NO:18. 
     
     
         34 . The method according to  claim 30 , wherein said isolated polynucleotides or oligonucleotides that recognize or modulate BAG3 protein expression are comprised in a vector. 
     
     
         35 . The method according to  claim 30  comprising genetically engineering a host cell with isolated polynucleotides or oligonucleotide/s that recognize or modulate BAG3 protein expression, said polynucleotides or oligonucleotides being selected from the group of nucleic acid sequences consisting of SEQ ID NO: 1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, and SEQ ID NO:11. 
     
     
         36 . The method according to  claim 35 , wherein said polynucleotides or oligonucleotides are in operative association with a regulatory sequence that controls expression of said polynucleotides or oligonucleotides in the host cell. 
     
     
         37 . The method according to  claim 31 , wherein said isolated polynucleotides or oligonucleotides with at least 90% homology to BAG3 SEQ ID NO:1 or fragments or a complementary sequence thereof, encode a peptide with SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, or SEQ ID NO:18 and modulate apoptosis in primary cells. 
     
     
         38 . A therapeutic method comprising the method for modulating apoptosis in a cell according to  claim 30  for the treatment of a disease involving excessive or defective apoptosis, said therapeutic method comprising administering to a subject in need thereof an effective amount of a polynucleotide or oligonucleotide selected from the group of nucleic acid sequences consisting of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10 and SEQ ID NO:11, or a sequence encoding a peptide of SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17 or SEQ ID NO:18 and fragments and complementary sequences thereof. 
     
     
         39 . The therapeutic method according to  claim 38 , wherein said disease involving excessive or defective apoptosis is selected from the group consisting of primary leukemias, acute or chronic tissue damage, such as heart, kidney, brain or other organ ischaemia, HIV-related damage of brain or other tissues, skeletal muscle disorders, transplantation rejection; chronic degenerative disorders such as Parkinson's disease, amyotrophic lateral sclerosis and others; and neoplastic, autoimmune and other diseases involving excessive or defective apoptosis; tissue repair or wound healing, treatment of surgical incisions, and ulcers, such as stomach or diabetic ulcers. 
     
     
         40 . The therapeutic method according to  claim 38 , wherein said subject in need thereof is under chemotherapeutic treatment. 
     
     
         41 . A method for detecting the presence of the nucleotide sequence SEQ ID NO:1 or parts thereof in a sample, said method comprising the steps of contacting the sample with a polynucleotide or oligonucleotide that binds to it and forms a complex with the nucleotide or parts thereof under conditions sufficient to form the complex, and detecting said complex. 
     
     
         42 . The method according to  claim 41 , wherein said part of SEQ ID NO:1 to which said polynucleotide or oligonucleotide binds is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10 and SEQ ID NO:11, or is a sequence encoding a peptide of SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17 and SEQ ID NO:18. 
     
     
         43 . A kit for identifying or diagnosing a disease involving excessive or defective apoptosis comprising at least one polynucleotide or nucleotide selected from the group consisting of SEQ ID NOS:1, 3, 5, 7, 9, 10 and 11 or a sequence encoding a peptide of SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17 and SEQ ID NO:18 fragments and a complementary sequence thereof.