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AssigneeCold Spring Harbor Laboratory
InventorsDavid H. Beach, Douglas J. Demetrick, Manuel Serrano, Gregory J. Hannon
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The present invention relates to the discovery in eukaryotic cells, particularly mammalian cells, of a novel family of cell-cycle regulatory proteins ("CCR-proteins"). As described herein, this family of proteins includes a polypeptide having an apparent molecular weight of 16 kDa, and a polypeptide having an apparent molecular weight of approximately 15 kDa, each of which can function as an inhibitor of cell-cycle progression, and therefore ultimately of cell growth. Thus, similar to the role of p21 to the p53 checkpoint, the subject CCR-proteins may function coordinately with the cell-cycle regulatory protein, retinoblastoma (RB). Furthermore, the CCR-protein family includes a protein having an apparent molecular weight of 13.5 kDa (hereinafter "p13.5"). The presumptive role of p13.5, like p16 and p15, is in the regulation of the cell-cycle.
An isolated nucleic acid encoding a polypeptide including an INK4 amino acid sequence which specifically binds to and inhibits a cyclin-dependent kinase (CDK), wherein said nucleic acid comprises a nucleotide sequence which hybridizes at conditions of 2.times.SSC at 50.degree. C. or higher stringency to a nucleic acid sequence of SEQ ID No:
An isolated nucleic acid encoding a polypeptide including an INK4 amino acid sequence wherein the nucleic acid comprises a nucleotide sequence which hybridizes at conditions of 2.times.SSC at 50.degree. C. or higher stringency to a nucleic acid sequence of SEQ ID No:
A nucleic acid composition comprising a substantially purified oligonucleotide at least 10-100 base pairs in length, which oligonucleotide is complementary to and which hybridizes under conditions of 2.times.SSC at 50.degree. C. or higher stringency to sense or antisense sequence of a nucleic acid encoding a human p16 polypeptide, or naturally occurring mutants thereof wherein said human p16 polypeptide specifically binds to a cyclin dependent kinase.
A recombinant transfection system, comprising
An isolated nucleic acid comprising a nucleotide sequence encoding a human p16 polypeptide, which polypeptide specifically binds a cyclin-dependent kinase (CDK).
An isolated nucleic acid comprising a nucleotide sequence which hybridizes under conditions of 2.times.SSC at 50.degree. C. or higher stringency to a human p16 gene and which encodes a polypeptide that specifically binds a cyclin-dependent kinase (CDK).
An isolated recombinant gene comprising a nucleotide sequence encoding a human p16 polypeptide having ankyrin-like repeats and capable of binding a cyclin dependent kinase, said nucleotide sequence being operably linked to a transcriptional regulatory sequence in an open reading frame and translatable to said human p16 polypeptide.
Dependencies are inferred from the claim text.