Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Patent
1995-02-16
1997-07-01
Chambers, Jasemine C.
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
530350, 530358, 536 241, C12Q 168, C07H 2104, A61K 3816, C07K 1447
Patent
active
056437277
ABSTRACT:
The present invention provides a bcl-2 gene inhibitory element (BIE), which can inhibit expression of a gene in position-dependent and orientation-dependent manner. The invention provides, for example, BIE-1, having the nucleotide sequence 5'-CAAGAATGCAA-3' (SEQ ID NO: 1), which acts in an orientation-dependent and position-dependent manner to down-regulate the expression of the bcl-2 gene. The invention also provides a BIE binding factor (BBF), which is a cellular factor that can bind to a BIE. The invention provides, for example, BBF-A, which binds to BIE-1, including a nucleic acid sequence (SEQ ID NO: 8) encoding a portion of the amino acid sequence (SEQ ID NO: 9) of BBF-A. The invention further provides an antibody that specifically binds BBF-A. The invention also provides screening assays for identifying agents that can increase or decrease the binding of a BBF to a BIE, modulate the expression of a nucleic acid molecule linked to a BIE or modulate apoptosis in a cell.
REFERENCES:
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Kamada et al. "A protein binding to CArG box motifs aand to single-stranded DNA functions as a transcriptional repressor", Gene 119: 229-236.
Miyashita, Toshiyuki et al. "Identification of p53-dependent Negative Response Element in the bcl-2 Gene." Canc. Res. 54:3131-3135 (1994a).
Miyashita, Toshiyuki et al., "Tumor Suppressor p53 is a Regulator of bcl-2 and bax Gene Expression in Vitro and In Vivo." Oncogene 9:1799-1805 (1994b).
Young, Robert L. and Korsmeyer, Stanley J. "A Negative Regulatory Element in the bcl-2 5'-Untranslated Region Inhibits Expression From an Upstream Promotor." Mol. Cell Biol. 13:3686-3697 (1993).
Khan, Farhat A., et al., "Cloning and Sequence Analysis of a Human Type A/B hnRNP Protein." Fed. Eur. Biochem. Soc. 290:159-161 (1991).
Dreyfuss, Gideon et al., "hnRNP Proteins and the Biogenesis of mRNA." Ann. Rev. Biochem. 62:289-321 (1993).
Harigai Masayoshi
Reed John C.
Chambers Jasemine C.
La Jolla Cancer Research Foundation
Priebe Scott D.
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