cDNA Encoding a Gene Bog (B5T Over-Expressed Gene) and its Protein Product
AssigneeThe Government of the United State, as represented by the Secretary, Dept. of Health & Human Service
InventorsSnorri S. Thorgeirsson, Joseph T. Woitach, Minghuang Zhang
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Abstract
Nucleic acids that encode novel polypeptides, designated in the present application as “BOG” (B5T Over-expressed Gene) are provided. BOG binds to pRb and is over-expressed in a number transformed rat liver epithelial (RLE) cell lines resistant to the growth inhibitory effect of TGF-β1 as well as in primary liver tumors. Compositions including BOG chimeras, nucleic acids encoding BOG and antibodies to BOG are also provided. Methods of using BOG to modulate pRb-protein interactions and to alter cellular phenotype are further provided.
Claims32
An isolated polypeptide comprising a BOG polypeptide fragment, said BOG fragment comprising a pRb binding motif and a casein kinase II phosphorylation motif.
An isolated nucleic acid encoding a BOG polypeptide fragment.
A BOG antisense oligonucleotide comprising a nucleotide sequence which is complimentary to an mRNA encoding a polypeptide comprising a BOG polypeptide fragment.
A chimeric molecule comprising a BOG polypeptide fragment fused to a heterologous amino acid sequence.
An isolated BOG specific polypeptide comprising an Fab fragment from an antibody capable of specifically binding to a BOG polypeptide fragment.
A method of assaying a sample for a BOG polypeptide fragment comprising detecting the presence or absence of said BOG polypeptide fragment in said sample utilizing an isolated BOG specific polypeptide which includes a Fab fragment from an antibody capable of specifically binding to the BOG polypeptide fragment.
A method of reducing BOG polypeptide fragment expression in a cell comprising exposing the cell to an oligonucleotide of at least about 15 nucleotides which are complementary to a BOG mRNA.
A method of inducing apoptosis in cells overexpressing BOG polypeptide fragments comprising exposing said cells to an effective amount of TGF-β and at least one BOG antisense oligonucleotide.
A method for producing cell lines having an altered phenotype comprising:
- (i) transfecting in vitro mammalian cells with a DNA vector encoding a BOG polypeptide fragment;
- (ii) expressing the BOG polypeptide fragment in said cells;
- and
- (iii) selecting for cells having an altered phenotype.
A method of inhibiting the interaction between a pRb A/B domain binding protein and a pRb family member comprising exposing the pRb family member to a BOG polypeptide fragment.
Dependencies are inferred from the claim text.