United States Patent 6,372,490
Nandabalan , et al. April 16, 2002
Nucleic acid encoding the MDM interacting protein
Abstract
Disclosed are complexes of the MDM2 protein and a novel MDM2-interacting protein (MDMIP). Also disclosed are nucleic acids encoding the MDMIP polypeptide, as well as derivatives, fragments, analogs and homologs of the MDMIP polypeptide and MDM2-MDMIP complexes.
Inventors: Nandabalan; Krishnan (Guilford, CT); Yang; Meijia (East Lyme, CT); Schulz; Vincent (Madison, CT)
Assignee: CuraGen Corporation (New Haven, CT)
Appl. No.: 510252
Filed: February 22, 2000
FIELD OF THE INVENTION
The invention relates generally to polypeptides and nucleic acids and more particularly to polypeptides that interact with the MDM2 polypeptide, and nucleic acids encoding these MDM2-interacting polypeptides.
BACKGROUND OF THE INVENTION
The gene MDM2 has been implicated in a variety of cellular processes. In addition, altered expression of MDM2 has been associated with several disease states, including cancer. For example, the MDM2 gene has been shown to be abnormally up-regulated in human tumors and tumor cell lines. In addition, amplification of MDM2 genes has been reported in a variety of cancers, e.g., human sarcoma, glioma, squamous cell carcinoma, breast cancer, astrocytoma, leukemia and lymphoma. These results indicate that the MDM2 protein plays a role in human carcinogenesis.
MDM2 has been reported to interact with, i.e., bind to other proteins. Some of these proteins have themselves been associated with tumorigenesis. For example, MDM2 has been reported to form a complex with the p53 tumor suppressor and to block the growth suppressive functions of p53. In addition, overexpression of MDM2 has been shown to block the transactivation, cell cycle arrest (S/G2 phase) and apoptotic functions of p53.
MDM2 has also been shown to interact with the retinoblastoma tumor suppressor protein pRb, and the E2F-1 and DP1 transcription factors. Through MDM2's activation of E2F and DP1, MDM2 is thought to stimulate a G1 to S transition in the cell cycle. In addition, MDM2 has also been reported to interact with Numb, a protein involved in the determination of cell fate. snip.... |
