Agents and methods for modulating activator protein-1-mediated cellular processes
AssigneeWisconsin Alumni Research Foundation
InventorsEmery H. Bresnick, Jason E. Norton, Jianlin Chu
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Abstract
Agents for modulating AP-1 mediated gene expression are provided. The modulating agents comprise an internalization moiety and: (1) a peptide sequence isolated from the intracellular domain of Notch-1 (NIC-1); or (2) a peptide analogue or peptidomimetic of the NIC-1 peptide sequence. Methods of using the modulating agents for modulating AP-1 mediated gene expression in a variety of contexts (e.g., for modulating inflammatory and immunosuppressive activities) are provided.
Claims22
A modulating agent for modulating AP-1 mediated cellular processes in a cell comprising an internalization moiety and one or more of:
- (a) an isolated polypeptide from the intracellular domain of Notch-1 (NIC-1) which is capable of modulating an AP-1 mediated cellular process;
- or
- (b) a peptide analog or peptidomimetic of the isolated polypeptide of (a) which is capable of modulating an AP-1 mediated response.
A method for modulating AP-1 mediated cellular processes in a cell, comprising contacting a cell with a composition including one or more of:
- (a) an isolated polypeptide from the intracellular domain of Notch-1 (NIC-1) which is capable of modulating an AP-1 mediated cellular process;
- or
- (b) a peptide analog or peptidomimetic of the isolated polypeptide of (a) which is capable of modulating an AP-1 mediated response;
- and thereby modulating an AP-1 mediated cellular process in the cell.
A method of identifying a Notch-1 intracellular (NIC-1) domain-derived modulating agent effective in modulating AP-1 mediated transcription comprising the steps of:
- (a) obtaining a cell line or organism transformed with a reporter gene operably linked to an AP-1 responsive element;
- (b) contacting said transformed cell line or organism with:
- (i) a polypeptide including a portion of the intracellular domain of Notch-1 (NIC-1);
- or
- (ii) a peptide analog or peptidomimetic of the polypeptide of (i);
- and
- (c) assaying the activity of the reporter gene wherein a statistically meaningful difference in the activity between the reporter gene in a transformed cell line or organism contacted with said portion of the NIC-1 domain, analog, or peptidomimetic thereof and the reporter gene in a transformed cell line or organism not contacted with said portion of the NIC-1 domain, analog, or peptidomimetic thereof correlates with the identification of a modulating agent.
Dependencies are inferred from the claim text.