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WO2005114188A3 - Cul4 e3 ligase mediators as regulators of p53 - Google Patents

Cul4 e3 ligase mediators as regulators of p53 Download PDF

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Publication number
WO2005114188A3
WO2005114188A3 PCT/US2005/014615 US2005014615W WO2005114188A3 WO 2005114188 A3 WO2005114188 A3 WO 2005114188A3 US 2005014615 W US2005014615 W US 2005014615W WO 2005114188 A3 WO2005114188 A3 WO 2005114188A3
Authority
WO
WIPO (PCT)
Prior art keywords
ubiquitination
cul4
activity
assays
ligase
Prior art date
Application number
PCT/US2005/014615
Other languages
French (fr)
Other versions
WO2005114188A2 (en
Inventor
Hui Zhang
Damon Powell Banks
Leigh Ann Aki Higa
Original Assignee
Univ Yale
Hui Zhang
Damon Powell Banks
Leigh Ann Aki Higa
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Univ Yale, Hui Zhang, Damon Powell Banks, Leigh Ann Aki Higa filed Critical Univ Yale
Publication of WO2005114188A2 publication Critical patent/WO2005114188A2/en
Publication of WO2005114188A3 publication Critical patent/WO2005114188A3/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/25—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving enzymes not classifiable in groups C12Q1/26 - C12Q1/66
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/90—Enzymes; Proenzymes
    • G01N2333/9015—Ligases (6)
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value
    • G01N2500/02—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)

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Zoology (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Molecular Biology (AREA)
  • Analytical Chemistry (AREA)
  • Biotechnology (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

The invention relates to assays for identifying modulators of p53­ubiquitination by CUL4 E3 ligase complexes. This assays allows detection of agents and compounds that affect p53 ubiquitination and thus, cell cycle regulation and cell survival in cells. In some assays, an increase in ubiquitination, in comparison to a test sample lacking a test compound, indicates a stimulation of p53 ubiquitination activity, whereas a reduction in p53 ubiquitination indicates an inhibitor of activity. The assays provided may be suited, for example, for high-throughput screening of agents. The invention further relates to methods of modulating p53 activity in a cell, such as a cell of a mammal, by administering agents which decrease expression or activity of a member of a CUL4 E3 ligase complex, or which block the binding of p53 to a CUL4 E3 ligase complex.
PCT/US2005/014615 2004-04-27 2005-04-27 Cul4 e3 ligase mediators as regulators of p53 WO2005114188A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US56570704P 2004-04-27 2004-04-27
US60/565,707 2004-04-27

Publications (2)

Publication Number Publication Date
WO2005114188A2 WO2005114188A2 (en) 2005-12-01
WO2005114188A3 true WO2005114188A3 (en) 2006-05-18

Family

ID=35115874

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2005/014615 WO2005114188A2 (en) 2004-04-27 2005-04-27 Cul4 e3 ligase mediators as regulators of p53

Country Status (1)

Country Link
WO (1) WO2005114188A2 (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2723169C (en) 2008-04-29 2020-06-30 Cornell University Substances and compositions for enhancing dna repair and methods of use
CN113278614B (en) * 2021-06-11 2022-11-18 新乡医学院 Regulatory factor for inhibiting ubiquitination of p53 protein and application thereof
WO2023235313A2 (en) * 2022-06-01 2023-12-07 The Broad Institute, Inc. Systems, compositions and methods for identifying e3 ligase substrates by ubiquitin biotinylation

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001097830A1 (en) * 2000-06-22 2001-12-27 Mount Sinai School Of Medicine Modification of mdm2 activity
WO2002024878A2 (en) * 2000-09-25 2002-03-28 Bayer Aktiengesellschaft Human e3 ubiquitin protein ligase-like enzyme
US20020168693A1 (en) * 1998-08-07 2002-11-14 California Institute Of Technology, A California Corporation Biochemical assay to monitor the ubiquitin ligase activities of cullins

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020168693A1 (en) * 1998-08-07 2002-11-14 California Institute Of Technology, A California Corporation Biochemical assay to monitor the ubiquitin ligase activities of cullins
WO2001097830A1 (en) * 2000-06-22 2001-12-27 Mount Sinai School Of Medicine Modification of mdm2 activity
WO2002024878A2 (en) * 2000-09-25 2002-03-28 Bayer Aktiengesellschaft Human e3 ubiquitin protein ligase-like enzyme

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
MIN KYOENG-WOO ET AL: "TIP120A associates with cullins and modulates ubiquitin ligase activity", J. BIOL. CHEM.; JOURNAL OF BIOLOGICAL CHEMISTRY MAY 2 2003, vol. 278, no. 18, 2 May 2003 (2003-05-02), pages 15905 - 15910, XP009056133 *
NAG ALO ET AL: "Cul4A physically associates with MDM2 and participates in the proteolysis of p53", CANCER RESEARCH, vol. 64, no. 22, 15 November 2004 (2004-11-15), pages 8152 - 8155, XP009056136, ISSN: 0008-5472 *

Also Published As

Publication number Publication date
WO2005114188A2 (en) 2005-12-01

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