University of California

The United States of America As Represented by the Department of Health

Keith R Yamamoto

Brian L West

John D Baxter

Peter J Kushner

Douglas Hanahan

Robert J Fletterick

Richard L Wagner

Pradip K Chakraborti

Samuel S Simons, Jr

Beatrice Darimont

Michael J Garabedian

Maria D Vivanco

Weijun Feng

Tristram G Parslow

The present invention relates to methods and agonist/antagonist compounds for modulating nuclear receptor coactivator binding. The invention includes a method for identifying residues comprising a coactivator binding site for a nuclear receptor of interest. Also included is a method of identifying agonists and/or antagonists that bind to a coactivator binding site of a nuclear receptor of interest. Agonists and antagonists of coactivator binding to nuclear receptors also are provided. The invention is exemplified by identification and manipulation of the coactivator binding site of the thyroid receptor (TR), and compounds that bind to this sites. The methods can be applied to other nuclear receptors including RAR, RXR, PPAR, VDR, ER, GR, PR, MR, and AR.

Methods for modulating nuclear receptor coactivator binding

Intracellular hormone receptors are discovered to undergo posttranslational regulation. Assays to assess cancer progression and to permit discovery of a new class of biologically active compounds are provided. Related kits are also provided.

Transition in transcriptional activation by intracellular hormone

The present invention relates to novel glucocorticoid receptors that have greater affinity and specifity for glucocorticoid steroids than the naturally occurring receptors. More particularly, the invention relates to the altering of the equivalent of cysteine-656 of the rat glucocorticoid receptor to either serine or glycine for the production of super glucocorticoid receptors which retain full biological activity in intact cells and have higher affinity and specificity for glucocorticoid steroid binding than the original receptor. The invention further relates to the recombinant expression of such altered receptors in host cells.

Super glucocorticoid receptors: receptors with increased affinity and

A mammalian myeloma cell comprising a double-stranded DNA molecule in its genome containing a coding sequence encoding a non-immunoglobulin protein, a non-immunoglobulin promoter sequence adjacent to the 5' terminus of said coding sequence, and the 8-base pair nucleotide sequence 5'-ATTTGCAT-3' located 5' to the transcription initiation site of said promoter sequence. The DNA molecule may optionally contain an enhancer element. Methods of producing non-immunoglobulin protein and DNA molecules are also provided.

Enhanced production of recombinant proteins in myeloma cells

Growing community of inventors

San Francisco, CA, United States of America

Keith R Yamamoto