Signal Pharmaceuticals, Inc.

Technion Research & Development Foundation Limited

Rappaport Family Institute for Research in the Medical Sciences

Yissum Research Development Company of the Hebrew University of Jerusalem Ltd.

Rockefeller Institute

Aaron J Ciechanover

Frank Mercurio

Yinon Ben-Neriah

Anthony M Manning

Avraham Yaron

Irit Alkalay

Matti Davis

Ada Hatzubai

Sharon Amit

Hedva Gonen

Sharo Amit

Yelena Kravtsova

Hermann Steller

Nava Blumenfeld

Gilad Goldhirsh

Hyung Don Ryoo

Inna Shomer

Victoria Cohen

A peptide comprising the amino acid sequence set forth in WILVRLW (SEQ ID NO: 1), or any functionally related variant thereof, a complex, conjugate or chimera comprising the same, wherein the peptide is linked with or without a linker to RING or to a molecule or peptide that recruits E3 ligase and method for treating cancer by administering the same.

Peptide, a complex and a method for treating cancer

The invention provides a method for treating cancer comprising the step of administering a therapeutically effective amount of KPC1, a peptide which is at least about 70% homologous to the KPC1 or an agent which up-regulates KPC1. In some embodiments, there is also provided a method for treating cancer comprising the step of administering a therapeutically effective amount of p50, a peptide which is at least about 70% homologous to the p50 or an agent which up-regulates p50.

Ubiquitin ligase KPC1 promotes processing of P105 NF-&#x3ba;B1 to p50, eliciting strong tumor suppression

Compositions and methods for modulating the activation of nuclear factor &#x3ba;B (NF-&#x3ba;B) are provided. The compositions comprise one or more agents that modulate ubiquitination of phosphorylated I&#x3ba;B&#x3b1; and/or I&#x3ba;B&#x3b2;. Such compositions may be used for treating diseases associated with NF-&#x3ba;B activation. Modulating agents include human E3 ubiquitin ligases, antibodies thereto and variants thereof, as well as related proteins.

Compounds and methods for modulating activation of NF-&#x3ba;B

The present invention provides novel peptides, nucleic acids, compounds, compositions and methods for regulating apoptosis, and screening methods for identifying same. Regulation of apoptosis is mediated via IAPi-derived proteins, peptide fragments thereof, and nucleic acids encoding same, stimulating/accelerating or downmodulating/suppressing apoptosis. For stimulation/acceleration of apoptosis, the IAPi-derived proteins or peptide fragments thereof comprise RHG and Trp-box amino acid consensus sequences. Stimulation/acceleration results in self-ubiquitination and auto-degradation of an IAP. For downmodulation/suppression of apoptosis, IAPi-derived proteins or peptide fragments thereof comprising either RHG or Trp-box amino acid consensus sequences, or both, failing to stimulate or suppressing self-ubiquitination and auto-degradation of an IAP, result in suppression of apoptosis.

Peptides and methods for cell death regulation

Compositions and methods for modulating the activation of nuclear factor &kgr;B (NF-&kgr;B) are provided. The compositions comprise one or more agents that modulate ubiquitination of phosphorylated I&kgr;B&agr; and/or I&kgr;B&bgr;. Such compositions may be used for treating diseases associated with NF-&kgr;B activation. Modulating agents include human E3 ubiquitin ligases, antibodies thereto and variants thereof, as well as related proteins.

Compounds and methods for modulating activation of NF-&kgr;B

Compositions and methods for modulating the activation of nuclear factor .kappa.B (NF-.kappa.B) are provided. The compositions comprise one or more agents that modulate ubiquitination of phosphorylated I.kappa.B.alpha. and/or I.kappa.B.beta.. Such compositions may be used for treating diseases associated with NF-.kappa.B activation. Modulating agents include peptides that comprise a recognition domain for E3 ubiquitin ligase.

Compositions and methods for modulating cellular NF-.kappa.B activation

A method for isolating and purifying novel species of E2 ubiquitin-carrier protein, designated E2-F1, is disclosed. A method for preparing enzymatically active fragments of E2-F1 enzyme is also disclosed. The use of purified E2-F1 to produce antibodies is also disclosed. The use of such E2-F1-specific antibodies to detect the presence of E2-F1 in a biological sample, and to inhibit protein degradation are also disclosed. Recombinant DNA molecules which code for E2-F1, and recombinant hosts and vectors which contain E2-F1 coding sequences are also disclosed. The use of such recombinant hosts and vectors to produce E2-F1 protein is also disclosed. The use of purified E2-F1 to identify and to isolate E3 enzyme is also disclosed. Methods for screening substances for the ability to inhibit E2-F1 enzyme activity are also disclosed.

Ubiquitin carrier enzyme E2-F1, purification, production, and use

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Haifa, Israel

Aaron J Ciechanover