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WO1999049042A1 - POINT DE CONTROLE DU CYCLE CELLULAIRE DE Rad1 D'ORIGINE HUMAINE - Google Patents

POINT DE CONTROLE DU CYCLE CELLULAIRE DE Rad1 D'ORIGINE HUMAINE Download PDF

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Publication number
WO1999049042A1
WO1999049042A1 PCT/US1999/006714 US9906714W WO9949042A1 WO 1999049042 A1 WO1999049042 A1 WO 1999049042A1 US 9906714 W US9906714 W US 9906714W WO 9949042 A1 WO9949042 A1 WO 9949042A1
Authority
WO
WIPO (PCT)
Prior art keywords
radl
ofthe
polypeptide
polynucleotide
dna
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/US1999/006714
Other languages
English (en)
Inventor
Daniel R. Herendeen
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Icos Corp
Original Assignee
Icos Corp
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 Icos Corp filed Critical Icos Corp
Priority to AU31179/99A priority Critical patent/AU3117999A/en
Publication of WO1999049042A1 publication Critical patent/WO1999049042A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4702—Regulators; Modulating activity
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A01K2217/07—Animals genetically altered by homologous recombination
    • A01K2217/075—Animals genetically altered by homologous recombination inducing loss of function, i.e. knock out
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2799/00—Uses of viruses
    • C12N2799/02—Uses of viruses as vector
    • C12N2799/021—Uses of viruses as vector for the expression of a heterologous nucleic acid
    • C12N2799/022—Uses of viruses as vector for the expression of a heterologous nucleic acid where the vector is derived from an adenovirus
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2799/00—Uses of viruses
    • C12N2799/02—Uses of viruses as vector
    • C12N2799/021—Uses of viruses as vector for the expression of a heterologous nucleic acid
    • C12N2799/027—Uses of viruses as vector for the expression of a heterologous nucleic acid where the vector is derived from a retrovirus

Definitions

  • antibodies e.g., monoclonal and polyclonal antibodies, single chain antibodies, chimeric antibodies, CDR-grafted antibodies and the like
  • other binding proteins specific for Radl products or fragments thereof.
  • the term "specific for” indicates that the variable regions of the antibodies ofthe invention recognize and bind Radl polypeptides exclusively or with high selectivity (i.e., able to distinguish distinct Radl polypeptides from the family of Rad 1 polypeptides despite sequence identity, homology, or similarity found in the family of polypeptides), but may also interact with other proteins (for example, S.
  • Polynucleotides ofthe invention may also be the basis for diagnostic methods useful for identifying a genetic alteration(s) in a Radl locus that underlies a disease state or states, including cancer (i.e., bladder, head and neck, cancers as well as small cell lung tumors), immune and proliferative disorders, cirrhosis, and rheumatoid arthritis.
  • cancer i.e., bladder, head and neck, cancers as well as small cell lung tumors
  • immune and proliferative disorders i.e., cirrhosis, and rheumatoid arthritis.
  • Radl polypeptide which contact polynucleotides, and (7) regions ofthe Radl polypeptide which possess enzymatic activity. Still other selective modulators include those that - 11 - recognize specific Radl encoding and regulatory polynucleotide sequences. Modulators of Radl activity may be therapeutically useful in treatment of a wide range of diseases and physiological conditions in which Radl activity is known, believed, or proposed to be involved as discussed herein. The present invention further embraces screening assays to identify modulators of Radl DNA binding, protein binding and exonuclease activities.
  • an agent which inhibits the transcription or the biological activity of Radl and thus the cell cycle checkpoint may be used to render cancerous cells more sensitive to chemotherapy or radiation therapy.
  • the therapeutic value of such an agent lies in the fact that current radiation therapy or chemotherapy in most cases does nothing to overcome the ability ofthe cancerous cell to sense and correct the DNA damage imposed as a result of the treatment. As a result, a cancer cell can simply repair the DNA damage.
  • Modulating agents of the invention may therefore be chemotherapy and radiation adjuvants or may be directly active as chemotherapeutic drugs themselves.
  • the hRadl mRNA was present in all tissues tested (spleen, thymus, prostate, testis, ovary, small intestine, colon, leukocyte, heart, brain, placenta, lung, liver, skeletal muscle, kidney, and pancreas) which would be expected for a gene with general cell cycle maintenance functions.
  • all cell lines HL-60, HeLa S3, K562, MOLT-4, Raji, SW480, A549, and G361
  • Endogenous proteins from human cell lines (30 and 37 kDa) were also detected in these assays.
  • GST-hRadl was also used to immunize 4 mice. Mice were initially immunized by subcutaneous injection of 40 ⁇ g GST-hRadl in Complete Freund's Adjuvant and boosted every three weeks with 20 ⁇ g
  • the - 29 - particles were removed by centrifugation for five minutes in an Eppendorf microfuge. Protein concentrations ofthe cell extracts were determined by Coomassie Plus reagent (Pierce) with BSA as the standard.
  • 3 ' end labeled pAdUAS (3 kbp plasmid linearized at single Ndel site) served as the substrate. Unincorporated label was removed by purifying DNA using Gene Clean II Kit (Bio 101) or by using Micro Bio spin columns (BioRad). Standard reaction conditions included 20 mM Tris-HCl (pH 8), 10 mM MgCl 2 , 1 mM DTT, and 1-30 ⁇ M (total nucleotide)substrate.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Biophysics (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Toxicology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

L'invention concerne de nouveaux polynucléotides de point de contrôle qui codent pour des polypeptides appelés Rad1, des polypeptides codés par les polynucléotides, des produits de recombinaison d'expression contenant les polynucléotides, des cellules hôtes transformées ou transfectées à l'aide des polynucléotides, des procédés de production des polypeptides, des anticorps immunospécifiques des polypeptides, des procédés d'identification de partenaires de liaison des polypeptides, et des procédés de criblage visant à rechercher des modulateurs de l'activité biologique de Rad1.
PCT/US1999/006714 1998-03-27 1999-03-29 POINT DE CONTROLE DU CYCLE CELLULAIRE DE Rad1 D'ORIGINE HUMAINE Ceased WO1999049042A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU31179/99A AU3117999A (en) 1998-03-27 1999-03-29 Human rad1 cell cycle checkpoint

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US4979298A 1998-03-27 1998-03-27
US09/049,792 1998-03-27

Publications (1)

Publication Number Publication Date
WO1999049042A1 true WO1999049042A1 (fr) 1999-09-30

Family

ID=21961767

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1999/006714 Ceased WO1999049042A1 (fr) 1998-03-27 1999-03-29 POINT DE CONTROLE DU CYCLE CELLULAIRE DE Rad1 D'ORIGINE HUMAINE

Country Status (2)

Country Link
AU (1) AU3117999A (fr)
WO (1) WO1999049042A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1620562A4 (fr) * 2003-04-11 2007-06-27 Univ Boston Modulation de signalisation cellulaire initiee par telomere
US8183222B2 (en) 1995-06-06 2012-05-22 Trustees Of Boston University Method to inhibit cell growth using oligonucleotides

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999031234A1 (fr) * 1997-12-16 1999-06-24 Kudos Pharmaceuticals Limited Acide nucleique rad1 de l'homme, polypeptides, dosages, procedes et moyens therapeutiques

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999031234A1 (fr) * 1997-12-16 1999-06-24 Kudos Pharmaceuticals Limited Acide nucleique rad1 de l'homme, polypeptides, dosages, procedes et moyens therapeutiques

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
FREIRE R ET AL: "Human and mouse homologs of Schizosaccharomyces pombe rad1+ and Saccharomyces cerevisiae RAD17: linkage to checkpoint control and mammalian meiosis", GENES AND DEVELOPMENT, vol. 12, no. 12, 15 August 1998 (1998-08-15), pages 2560 - 2573, XP002098400, ISSN: 0890-9369 *
HILLIER L ET AL: "The WashU-NCI human EST Project, ab35b05.r1 Homo sapiens cDNA clone 842769 5' similar to SW:RAD1_SCHPO P22193 DNA REPAIR PROTEIN RAD1", MATERIALS SCIENCE AND ENGINEERING B, XP002111462, ISSN: 0921-5107 *
HILLIER L. ET AL.: "The WashU-Merck EST Project 1997, zr56h11.r1 NhHMPu S1 Homo sapiens cDNA clone 667461 5'", EMBL DATABASE ENTRY HS1147325; ACCESSION NUMBER AA227739, 12 February 1997 (1997-02-12), XP002111463 *
HILLIER L. ET AL.: "The WashU-Merck EST Project, zk10c07.s1 Soares pregnant uterus NbHPU Homo sapiens cDNA clone 470124 3' similar to SW:RAD1_SCHPO P22193 DNA REPAIR PROTEIN RAD1", EMBL DATABASE ENTRY HSA29300; ACCESSION NUMBER AA029300, 25 June 1997 (1997-06-25), XP002111135 *
MARRA M. ET AL.: "The WashU-HHMI Mouse EST Project, mx23e05.r1 Soares mouse NML Mus musculus cDNA clone 681056 5'", EMBL DATABASE ENTRY MM1165167, ACCESSION NUMBER AA250088, 15 March 1997 (1997-03-15), XP002111492 *
MARRA M. ET AL.: "The WashU-HHMI Mouse EST Project, va52g09.r1 Soares mouse 3NME12 5 Mus musculus cDNA clone 735040 5'", EMBL DATABASE ENTRY MMAA60182, ACCESSION NUMBER AA260182, - 19 March 1997 (1997-03-19), XP002111493 *
PARKER A. E. ET AL.: "A Human Homologue of the Schizosaccharomyces pombe rad1+ Checkpoint Gene Encodes an Exonuclease", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 29, no. 17, 17 July 1998 (1998-07-17), pages 18332 - 18339, XP002111392 *
UDELL C ET AL: "HRAD1 and MRAD1 encode mammalian homologues of the fission yeast rad1+ cell cycle checkpoint control gene", NUCLEIC ACIDS RESEARCH, vol. 26, no. 17, 1 September 1998 (1998-09-01), pages 3971 - 3976, XP002098401, ISSN: 0305-1048 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8183222B2 (en) 1995-06-06 2012-05-22 Trustees Of Boston University Method to inhibit cell growth using oligonucleotides
EP1620562A4 (fr) * 2003-04-11 2007-06-27 Univ Boston Modulation de signalisation cellulaire initiee par telomere

Also Published As

Publication number Publication date
AU3117999A (en) 1999-10-18

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