Interaction between cyclin D1 and steroid receptor co-activators and uses thereof in assays
AssigneeProlifix Limited
InventorsRene Bernards, Renate Zwijsen
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Abstract
The present invention relates to the finding that cyclin D1 interacts in a ligand-independent fashion with coactivators of the SRC-1 family. The direct interaction of cyclin D1 enhances estrogen receptor (ER) mediated transcription and provides a novel target for the development of assays for substances which modulate the cell cycle. The invention provides assay methods for the prevention of growth of tumors, for assays for compounds useful in the prevention of tumors and compounds obtainable by such assays.
Claims11
An assay for a modulator of estrogen responsive tumour cells which comprises:
- a) bringing into contact a cyclin D1, an SRC and a putative imodulator compound under conditions where the cyclin D1 and the SRC, in the absence of inhibitor, are capable of forming a complex;
- and
- b) measuring the degree of inhibition of complex formation caused by said modulator compound.
An assay for a modulator of estrogen responsive tumour cells which comprises:
- a) bringing into contact a cyclin D1, an SRC, an estrogen receptor and a putative inhibitor compound under conditions where the cyclin, the SRC and the estrogen receptor, in the absence of inhibitor, are capable of forming a complex which is capable of binding to an estrogen response element;
- b) providing an estrogen response element to which the complex is capable of binding and transcriptionally activating;
- and
- c) measuring the degree of inhibition of binding or transcriptional activation caused by said inhibitor compound.
An peptide of formula:
- Z1-LXXLL-Z2
- where z1 is an N-terminal of a sequence of from 1 to 8 amino acids, and z2 is a C-terminal or sequence of from 1 to 8 amino acids.
A peptide of a formula selected from the group:
- 3 A A S K H K Q L S E L L R S G (SEQ ID NO:1) S H K L V Q L L T T T A E Q (SEQ ID NO:2) E R H K I L H R L L Q E G S (SEQ ID NO:3) K D H Q L L R L L D K D E (SEQ ID NO:4);
- and P Q A Q Q K S L Q Q L L T (SEQ ID NO:5)
Dependencies are inferred from the claim text.