Novel card proteins involved in cell death regulation

Abstract

The present invention provides NB-ARC and CARD-containing proteins (NACs), nucleic acid molecules encoding NACs and antibodies specific for at least one NAC. The invention further provides chimeric NAC proteins. The invention also provides screening assays for identifying an agent that can effectively alter the association of a NAC with a NAC-associated protein. The invention further provides methods of modulating apoptosis in a cell by introducing into the cell a nucleic acid molecule encoding a NAC or an antisense nucleotide sequence. The invention also provides a method of using a reagent that can specifically bind to a NAC to diagnose a pathology that is characterized by an increased or decreased level of apoptosis in a cell.

Description

[0001] This application is a divisional of U.S. Ser. No. 09 / 388,221, filed Sep. 1, 1999, which is incorporated herein by reference in its entirety.[0002] This invention relates generally to the fields of molecular biology and molecular medicine and more specifically to the identification of proteins involved in programmed cell death and associations of these proteins.BACKGROUND INFORMATION[0003] Programmed cell death is a physiologic process that ensures homeostasis is maintained between cell production and cell turnover in essentially all self-renewing tissues. In many cases, characteristic morphological changes, termed "apoptosis," occur in a dying cell. Since similar changes occur in different types of dying cells, cell death appears to proceed through a common pathway in different cell types.[0004] In addition to maintaining tissue homeostasis, apoptosis also occurs in response to a variety of external stimuli, including growth factor deprivation, alterations in calcium levels, ...

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Benefits of technology

[0010] The present invention also provides a screening assay useful for identifying agents that can effectively alter the association of NAC with itself or with other proteins. By altering the self-association of NAC or by altering their interactions with other proteins, an effective agent may increase or decrease the level of caspase proteolytic activity or apoptosis in a cell, or it may increase or decrease the levels of NF-.kappa.B, cytokine production, or other events.

[0011] The invention also provides methods of altering the activity of NAC in a cell, wherein such increased or decreased activity of NAC can modulate the level of apoptosis or other cellular responses. For example, the activity of NAC in a cell can be increased by introducing into the cell and expressing a nucleic acid sequence encoding these proteins. In addition, the activity of NAC in a cell can be decreased by introducing into the cell and expressing a fragment of NAC, or an antisense nucleotide sequence that is complementary to a portion of a nucleic acid molecule encoding the NAC proteins.

Problems solved by technology

For example, a NAC which does not induce apoptosis may form hetero-oligomers with a NAC which is apoptotic, thus interfering with the apoptosis-inducing activity of NAC.

Although such polypeptides are considered NAPs or CAPs, it is well known that a cDNA sequence obtained from a cDNA library may not encode the full length protein.

An increase or decrease in the steady state level of association of NAP and NAC proteins in a cell can result in an increased or decreased level of apoptosis in the cell, which can result in a pathology in a subject.

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