Methods and compositions relating to promoter regulation by MUC1 and KLF proteins

• US 8,012,695 B2
• Filed: 02/14/2008
• Issued: 09/06/2011
• Est. Priority Date: 02/14/2007
• Status: Expired due to Fees

• Current Assignee: Dana-Farber Cancer Institute
• Original Assignee: Dana-Farber Cancer Institute
• Inventors: Kufe, Donald W.
• Primary Examiner(s): NOAKES, SUZANNE MARIE
• Application Number:
  US12/031,316
• Publication Number:
  US 20090098054A1
• Time in Patent Office: 1,300 Days
• Field of Search: None
• US Class Current: 435/7.1
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: G01N 2333/4704 Inhibitors; Supressors
• CPC Class Codes: G01N 2333/4725 Mucins, e.g. human intestinal mucin
• CPC Class Codes: G01N 2333/4748 p53
• CPC Class Codes: G01N 2500/02 Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor)
• CPC Class Codes: G01N 33/6872 Intracellular protein regulatory factors and their receptors, e.g. including ion channels

Abstract

This invention relates to regulation of cell signaling, cell growth, and more particularly to the regulation of cancer or inflammatory cell growth and/or activation. The invention provides methods of, and compositions useful for, inhibiting interactions between MUC1 and a kruppel-like factor (KLF), method of inhibiting interactions between a KLF protein and the p53 promoter, methods of inhibiting the interaction between MUC1 and the p53 promoter, methods of increasing p53 activity, and methods of increasing histone acetylation. The invention also provides screening methods for identifying compounds that inhibit the aforementioned interactions. Pharmaceutical compositions containing the identified compounds can be useful in treating cancers and inflammatory conditions.

Claims

1. A method of identifying a compound that inhibits the binding of MUC1 to a kruppel-like factor (KLF), the method comprising:

(a) contacting a MUC1 peptide segment comprising the MUC1 cytoplasmic domain (MUC1-CD) comprising SEQ ID NO;

3 with a KLF4 peptide segment comprising SEQ ID NO;

7 in the presence of a candidate compound; and

(b) determining whether the candidate compound inhibits binding of the MUC1 peptide segment to the KLF peptide segment.

2. The method of claim 1, wherein the contacting of the MUC1 peptide segment with the KLF peptide segment in the presence of the candidate compound occurs in the further presence of a p53 promoter reagent comprising a PE21 element.