P40 protein acts as an oncogene
AssigneeThe Johns Hopkins University
InventorsDavid Sidransky, Jin Jen, Barry Trink, Edward A. Ratovitski
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AssigneeThe Johns Hopkins University
InventorsDavid Sidransky, Jin Jen, Barry Trink, Edward A. Ratovitski
Estimating the term…
We have discovered p40, the shortest variant of a new human p53 homologue (p40/p51/p63/p73H). We have also found that it plays a role in cancer. Low level amplification of the p40 locus accompanied by RNA and protein overexpression was observed in primary lung cancers, and head and neck cancer cell lines. P40 protein overexpression in primary lung tumors was limited to squamous cell carcinoma, tumors known to harbor a high frequency of p53 mutations. Overexpression of p40 in Rat 1a cells led to an increase in soft agar growth and tumor size in mice. We searched for p40 binding proteins using the yeast two-hybrid system. P53 was the most common binding target of the 1.6×106 clones screened from a mouse embryonic library. Moreover, coexpression of p40 and p53 led to a decrease in p53 transcriptional activity. Our results support the notion that p40 plays an oncogenic role in human cancer.
An isolated and purified p40 protein having an amino acid sequence which is at least 99% identical to SEQ ID NO:2, wherein percent identity is determined using a Smith-Waterman homology search algorithm using an affine gap search with a gap open penalty of 12 and a gap extension penalty of 1.
A p40 fusion protein comprising a first protein segment and a second protein segment fused together by means of a peptide bond, wherein the first protein segment consists of a p40 protein as shown in SEQ ID NO:2.
A preparation of antibodies which specifically bind to a p40 protein having an amino acid sequence as shown in SEQ ID NO:2, but which does not bind to p53 as shown in SEQ ID NO:
A cDNA molecule which encodes a p40 protein having an amino acid sequence which is at least 99% identical to SEQ ID NO:2, wherein percent identity is determined using a Smith-Waterman homology search algorithm using an affine gap search with a gap open penalty of 12 and a gap extension penalty of 1.
A cDNA molecule which is at least 99% identical to the nucleotide sequence shown in SEQ ID NO:1, wherein percent identity is determined using a Smith-Waterman homology search algorithm using an affine gap search with a gap open penalty of 12 and a gap extension penalty of 1.
A nucleic acid construct comprising:
A host cell comprising a nucleic acid construct which comprises:
A method of diagnosing a neoplastic tissue of a human, comprising the step of:
A method of identifying or classifying a neoplastic tissue of a human, comprising the step of:
A method of screening test compounds for the ability to modulate the binding of a p40 protein to a p53 protein, comprising the steps of:
A method of screening test compounds for the ability to modulate the binding of a p53 protein to a p40 protein, comprising the steps of:
A cell which comprises three recombinant DNA constructs, wherein a first construct encodes a first polypeptide fused to a sequence-specific DNA-binding domain, wherein a second construct encodes a second polypeptide fused to a transcriptional activation domain, and wherein a third construct comprises a reporter gene downstream from a DNA element which is recognized by the sequence-specific DNA-binding domain, wherein the first polypeptide comprises a p40 protein as shown in SEQ ID NO:2 and the second polypeptide comprises a p53 protein as shown in SEQ ID NO:4, or the first polypeptide comprises a p53 protein as shown in SEQ ID NO:4 and the second polypeptide comprises a p40 protein as shown in SEQ ID NO:2.
A method of visualizing a human chromosomal arm 3q, comprising the steps of:
A therapeutic composition for treating neoplasia, comprising:
A therapeutic composition comprising:
A method of treating neoplasia, comprising the step of:
Dependencies are inferred from the claim text.