Cold Spring Harbor Laboratory

Other

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Albert Einstein College of Medicine

Mitotix, Inc.

Gpc Biotech, Inc.

Cold Spring Harbor

Cold Spring Harbor Labs.

Cold Spring Habor Labortary

David H Beach

Gregory J Hannon

Manuel Serrano

Konstantin Galaktionov

Douglas J Demetrick

Jeno Gyuris

Lou Lamphere

Maureen G Caligiuri

Bradley Nefsky

Charles J Sherr

Douglas S Conklin

Ronald A DePinho

Scott Hammond

Dawn E Quelle

Emily Bernstein

Amy Caudy

Peiqing Sun

Catherine Jessus

Hui Zhang

The present invention provides methods for attenuating gene expression in a cell using gene-targeted double stranded RNA (dsRNA). The dsRNA contains a nucleotide sequence that hybridizes under physiologic conditions of the cell to the nucleotide sequence of at least a portion of the gene to be inhibited (the 'target' gene).

Methods and compositions for RNA interference using recombinant Dicer and Argonaut

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

Two previously undescribed human cdc25 genes, designated cdc25 A and cdc25 B, which have been shown to have an endogenous tyrosine phosphatase activity that can be specifically activated by B-type cyclin, in the complete absence of cdc2 are described. As a result of this work, new approaches to regulating the cell cycle in eukaryotic cells and, particularly, to regulating the activity of tyrosine specific phosphatases which play a key role in the cell cycle are available. Applicant's invention relates to methods of regulating the cell cycle and, specifically, to regulating activation of cdc2-kinase, through alteration of the activity and/or levels of tyrosine phosphatases or through alteration of the interaction of components of MPF. More specifically, the invention relates to inhibiting transcription or translation of mammalian CDC25A genes using oligonucleotides.

Cdc25 genes, encoded products and uses thereof

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 of a ubiquitin ligases. These proteins are referred to herein collectively as &ldquo;pub&rdquo; proteins for Protein UBiquitin ligase, and individually as h-pub1, h-pub2 and s-pub1 for the human pub1 and pub2 and pub1 clones, respectively. Pub1 proteins apparently play a role in the ubiquitination of the mitotic activating tyrosine phosphatase cdc25, and thus they may regulate the progression of proliferation in eukaryotic cells by activating the cyclin dependent kinase complexes. In disruption of s-pub1 elevates the level of cdc25 protein in vivo increasing the activity of the tyrosine kinases, wee1 and mik1, required to arrest the cell-cycle. Loss of wee1 function in an cell carrying a disruption in the s-pub1 gene results in a lethal premature entry into mitosis; such lethal phenotype can be rescued by the loss of cdc25 function. An ubiquitin thioester adduct of s-pub1 can be isolated from and disruption of s-pub1 dramatically reduces ubiquitination of cdc25.

Ubiquitin ligases and uses related thereto

The present invention pertains to novel inhibitors of cyclin-dependent kinases (CDKs), particularly CDK/cyclin complexes, which inhibitors can be used to control proliferation and/or differentiation of cells in which the inhibitors are introduced.

Inhibitors of cell-cycle progression 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 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 makes available assays and reagents for identifying agents which can be used to modulate at least one proliferation, differentiation and cell death by apoptosis.

Assays and reagents for identifying modulators of Cdc25-mediated mitotic activation

Mammalian viral vectors and their uses

A novel class of cyclins, referred to as D-type cyclins, of mammalian origin, particularly human origin, DNA and RNA encoding the novel cyclins, and a method of identifying other D-type and non-D type cyclins. Also disclosed are a method of detecting an increased level of a D-type cyclin and a method of inhibiting cell division by interfering with formation of the protein kinase-D type cyclin complex essential for cell cycle start.

Growing community of inventors

Huntington Bay, NY, United States of America

David H Beach