Cold Spring Harbor Laboratory

Albert Einstein College of Medicine

Cold Spring Harbor

Cold Spring Habor Labortary

Manuel Serrano

David H Beach

Gregory J Hannon

Douglas J Demetrick

Charles J Sherr

Ronald A DePinho

Dawn E Quelle

The present invention relates to the discovery in eukaryotic cells, particularly mammalian cells, of a 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. The present invention comprises antibodies directed to such CCR-proteins. The present invention is directed to a kit for detecting the level of cyclin-dependent kinase inhibitor p16 gene expression comprising antibodies directed to a p16 protein.

Kit for detecting the level of cyclin-dependent kinase inhibitor P16 gene expression

The present invention relates to the discovery in eukaryotic cells, particularly human cells, a novel polypeptide of 16 kDa (hereinafter 'p16' or 'p16') can function as an inhibitor of cell cycle progression, and therefore ultimately of cell growth, and that similar to the role of p21 and p53, the p16 protein may function coordinately with the cell cycle regulatory protein, retinoblastoma (Rb).

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The present invention relates to the discovery in eukaryotic cells, particularly mammalian cells, of a 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. The present invention comprises antibodies directed to such CCR-proteins.

Antibodies to the cell cycle regulatory protein p16

The present invention relates to the discovery in eukaryotic cells, particularly mammalian cells, of mutant cyclin dependent kinase (CDK) proteins. These proteins fail to bind to CDK-inhibitory proteins and thus lead to aberrant cell growth. Herein, screening assays are described to identify CDK mutant proteins and the uses of these mutant proteins as tumor vaccines is described.

Cyclin dependent kinase mutants, and diagnostic and therapeutic uses related thereto

The present invention relates to the discovery in eukaryotic cells, particularly mammalian cells, of a novel family of cell-cycle regulatory proteins (&ldquo;CCR-proteins&rdquo;). 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 &ldquo;p13.5&rdquo;). The presumptive role of p13.5, like p16 and p15, is in the regulation of the cell-cycle.

Cell-cycle regulatory proteins, and uses related thereto

The present invention relates to the discovery in eukaryotic cells, particularly mammalian cells, of a novel family of cell-cycle regulatory proteins (&ldquo;CCR-proteins&rdquo;). As described herein, this family of proteins is characterized by four ankyrin repeats and the ability to bind to a cyclin dependent kinase (CDK). The family 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).

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 is characterized by four ankyrin repeats and the ability to bind to a cyclin dependent kinase (CDK). The family 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).

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.

The present invention relates to transgenic mice in which the biological function of at least one cell cycle regulatory proteins of the INK4 family is altered.

Transgenic mice having modified cell-cycle regulation

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, these family of proteins includes a polypeptide having an apparent molecular weight of 16 kDa (hereinafter 'p16.sup.INK4 ' OR 'p16') and which can function as an inhibitor of cell-cycle progression, and therefore ultimately of cell growth, and that similar to role of p21 and p53, the p16 protein 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, is in the regulation of the cell-cycle.

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Mill Neck, NY, United States of America

Manuel Serrano