Mitotix, Inc.

Gpc Biotech, Inc.

Mark Rolfe

Giulio Draetta

Guillaume Cottarel

Peggy L Beer-Romero

Veronique Damagnez

Vivian Berlin

Maria Isabel Chiu

Jens W Eckstein

Maureen Caligiuri

Peter J Strack

Susan J Glass

The present invention relates to the discovery in eukaryotic cells, particularly human cells, of novel protein-protein interactions between certain cellular proteins, referred to herein as 'E6AP-binding proteins' or 'E6AP-BPs', and the cellular protein E6AP, the latter of which is a component of a ubiquitin-ligase (E3) enzyme. The association of E6AP and the subject E6AP-binding proteins implicates the E6AP-binding proteins in a number of basic cellular functions, such as regulation of gene expression, regulation of the cell-cycle, modification of cell surface receptors, biogenesis of ribosomes, and DNA repair. One of the E6AP-binding proteins shares certain homology with the papillomavirus E6 protein, which also binds E6AP.

E6AP-binding proteins

The present invention relates to the isolation of a new class of ubiquitin ligases involved in protein degradation in vertebrate organisms, such as protein degradation of cell cycle regulatory proteins. Accordingly, the invention provides nucleic acids and the proteins encoded by said nucleic acids which play a role in the ubiquitinylation and subsequent degradation of substrate proteins and in regulating cell proliferation, cell differentiation, and cell survival. The invention also provides methods for modulating protein degradation, cell proliferation, cell differentiation and/or cell survival by modulating protein ubiquitination; assays for identifying compounds which modulate protein degradation, cell proliferation, differentiation and/or cell survival; methods for treating disorders associated with aberrant protein degradation, cell proliferation, cell differentiation, and/or cell survival; and diagnostic and prognostic assays for determining whether a subject is at risk of developing a disorder associated with an aberrant protein degradation, cell proliferation, cell differentiation, and/or survival.

Components of ubiquitin ligase complexes, and uses related thereto

The present invention relates to drug screening assays which provide a systematic and practical approach for the identification of candidate agents able to inhibit ubiquitin-mediated degradation of a cell-cycle regulatory protein, such as p53, p27, myc, fos, MAT.alpha.2, or cyclins. The invention further relates to novel ubiquitin-conjugating enzymes, and uses related thereto.

Ubiquitin conjugating enzymes

The present invention relates to drug screening assays which provide a systematic and practical approach for the identification of candidate agents able to inhibit ubiquitin-mediated degradation of I.kappa.B and other I.kappa.B-related polypeptides.

Regulation of I Kappa B (I.kappa.B) degradation and methods and reagents

The present invention concerns a novel human ubiquitin-conjugating enzyme which is implicated in the ubiquitin-mediated inactivation of cell-cycle regulatory proteins, partucularly p53. The present invention makes available diagnostic and therapeutic assays and reagents for detecting and treating transformed cells, such as may be useful in the detection of cancer. The present invention also provides reagents for altering the normal regulation cell proliferation in untransformed cells, such as by upregulating certain cell-cycle checkpoints, e.g. to protect normal cells against DNA damaging reagents.

Human ubiquitin conjugating enzyme

The present invention relates to the discovery that antisense nucleic acids complimentary to an E6AP gene can be used to regulate cellular p53 levels. In general the invention features E6AP antisense constructs which, by inhibiting E6AP activity, can modulate cellular p53 levels in both p53+ transformed cells and in normal cells. The invention also provides methods for treating papillomavirus (PV) induced condition, methods for regulating cellular p53 levels and methods for regulating cellular proliferation.

E6AP antisense constructs and methods of use

The present invention concerns three ubiquitin-conjugating enzymes.

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Newton Upper Falls, MA, United States of America

Mark Rolfe