Isolated nucleic acid molecules encoding a bacterial uracil transport protein and a bacterial uracil phosphoribosyl-transferase enzyme, cells transformed therewith and uses thereof
View Patent ↗Disclosed herein are novel polynucleotides encoding one of a uracil transport protein and a uracil phosphoribosyl transferase, each being derived from Salmonella typhimurium. The disclosed uracil phosphoribosyl transferase protein is useful in sensitizing human cancer cells to treatment with anti-cancer agents such as 5-Fluorouracil.
1. An isolated nucleic acid molecule, comprising a sequence of nucleotides that encodes a uracil transport protein, wherein the sequence of nucleotides is selected from the group consisting of:
(a) a sequence of nucleotides as set forth in SEQ ID NO:1;
(b) a sequence of nucleotides that encode a protein having an amino acid sequence as set forth in SEQ ID NO:3;
(c) a sequence of nucleotides degenerate with the uracil transport protein encoding sequence of (a) or (b).
2. The isolated nucleic acid molecule according to claim 1 wherein said nucleic acid molecule encodes a polypeptide comprising the amino acid sequence as set forth in SEQ ID NO:3.
3. The isolated nucleic acid molecule comprising the nucleotide sequence as set forth in SEQ ID NO:1.
4. An expression vector comprising a nucleic acid molecule comprising the sequence of nucleotides as set forth in SEQ ID NO:1, operably linked to a regulatory nucleotide sequence that controls expression of the nucleic acid molecule in a host cell.
5. Host cells transformed or transfected with the nucleic acid molecule of claim 4 .
6. A method for identifying DNA sequences encoding a uracil transport protein of bacterial origin, the method comprising probing a cDNA library or a genomic library with a labeled probe comprising the nucleotide sequence of SEQ ID NO:1, and recovering from the library those sequences having a significant degree of homology relative to the probe.
7. A substantially pure polypeptide encoded by the nucleic acid molecule according to claim 1 , which comprises the amino acid sequence as set forth in SEQ ID NO.3.
8. The nucleic acid molecule method according to claim 1 , wherein the nucleic acid sequence comprises a coding region from nucleotides 215 to 841 of SEQ ID NO: 1.