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WO1999000499A1 - Proteine humaine interagissant avec fadd (fip) - Google Patents

Proteine humaine interagissant avec fadd (fip) Download PDF

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Publication number
WO1999000499A1
WO1999000499A1 PCT/US1998/013320 US9813320W WO9900499A1 WO 1999000499 A1 WO1999000499 A1 WO 1999000499A1 US 9813320 W US9813320 W US 9813320W WO 9900499 A1 WO9900499 A1 WO 9900499A1
Authority
WO
WIPO (PCT)
Prior art keywords
fip
flp
cell
ofthe
protein
Prior art date
Application number
PCT/US1998/013320
Other languages
English (en)
Inventor
Tseng-Hu Timothy Chen
Lewis T. Williams
Original Assignee
Chiron Corporation
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 Chiron Corporation filed Critical Chiron Corporation
Priority to AU79886/98A priority Critical patent/AU7988698A/en
Publication of WO1999000499A1 publication Critical patent/WO1999000499A1/fr

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Classifications

    • 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
    • C07K14/4747—Apoptosis related proteins
    • 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

Definitions

  • Full-length human FLP has the sequence disclosed in SEQ LD NO:2. Any naturally occurring biologically active variants of this sequence which occur in human tissues are within the scope of this invention. Naturally occurring biologically active variants of full-length FLP bind to FADD, are expressed in at least one human tissue, and do not induce apoptosis. Naturally occurring biologically active variants of FLP ⁇ . ⁇ bind to FADD, are found in brain, pancreas, peripheral blood lymphocytes, and spleen, and induce apoptosis.
  • Percent sequence identity between the sequence of a wild-type subgenomic polynucleotide and a homologous nucleotide sequence is calculated by counting the number of nucleotide matches between the wild-type and the homolog and dividing the total number of matches by the total number of nucleotides ofthe wild-type sequence.
  • homologous FIP sequences can be confirmed by hybridization under stringent conditions, as is known in the art.
  • FIP subgenomic polynucleotides can be isolated and purified free from other nucleotide sequences using standard nucleic acid purification techniques. For example, restriction enzymes and probes can be used to isolate polynucleotide fragments which comprise nucleotide sequences encoding a FLP protein. Isolated and purified subgenomic polynucleotides are in preparations which are free or at least 90% free of other molecules.
  • the gene delivery vehicle comprises a promoter and a FIP subgenomic polynucleotide.
  • Preferred promoters are tissue-specific promoters and promoters which are activated by cellular proliferation, such as the thymidine kinase and thymidylate synthase promoters.
  • Other preferred promoters include promoters which are activatable by infection with a virus, such as the ⁇ - and ⁇ -interferon promoters, and promoters which are activatable by a hormone, such as estrogen.
  • Other promoters which can be used include the Moloney virus LTR, the CMV promoter, and the mouse albumin promoter.
  • retrovector LTRs can be derived from a murine sarcoma virus, a tRNA binding site from a Rous sarcoma virus, a packaging signal from a murine leukemia virus, and an origin of second strand synthesis from an avian leukosis virus.
  • retroviral vectors can be used to generate transduction competent retroviral vector particles by introducing them into appropriate packaging cell lines (see Serial No. 07/800,921, filed November 29, 1991).
  • Recombinant retroviruses can be produced which direct the site-specific integration ofthe recombinant retroviral genome into specific regions ofthe host cell DNA.
  • a FIP gene delivery vehicle is derived from a togavirus.
  • Preferred togaviruses include alphaviruses, in particular those described in U.S. Serial No. 08/405,627, filed March 15, 1995, WO
  • 727 is decreased by at least 90%, 95%, 99%, or 100%.
  • the effectiveness ofthe mechanism chosen to decrease the can be assessed using methods well known in the art, such as hybridization of nucleotide probes to FIP mRNA, quantitative RT-PCR, or detection of FIP protein using FLP-specific antibodies of the invention.
  • a portion of a FJLP protein which induces apoptosis can be identified, and that portion or a nucleotide sequence encoding it can be introduced into the cell.
  • Portions of a which induce apoptosis can be identified by introducing expression constmcts which express different portions of the protein into cells and observing increased apoptosis, as described in Example 4, below.
  • the targeting sequence is a segment of at least 10, 12, 15, 20, or 50 contiguous nucleotides selected from the nucleotide sequence shown in SEQ LD
  • coli lacZ gene whose expression can be measured colorimetrically (e.g., Fields and Song, supra), and yeast selectable genes such as HIS3 (Harper et al, supra; Votjet et al, supra; Hannon et al, supra) or URA3 (Le Douarin et al, supra).
  • yeast selectable genes such as HIS3 (Harper et al, supra; Votjet et al, supra; Hannon et al, supra) or URA3 (Le Douarin et al, supra).
  • Methods for transforming cells are also well known in the art. See, e.g., Hinnen et al, Proc. Natl. Acad Sci. U.S.A. 75, 1929- 1933, 1978.
  • FLP amino acids can be detected, for example, using FLP-specific antibodies in Western blots.
  • the body sample is assayed for the presence of a.
  • Such mRNA has a size of about 2.5 kb.
  • Subgenomic polynucleotides ofthe invention can be radiolabeled or labeled with fluorescent or enzymatic tags and used to detect FIP mRNA in Northern blots.
  • kb FIP mRNA indicates that the body sample originates from either brain, pancreas, spleen, or peripheral blood lymphocytes, all of which express
  • the body sample can be normal tissue or can be a tumor.
  • the tumor can be a metastatic lesion. Determination of the origin of a tumor or metastatic lesion is useful in selecting appropriate therapeutic interventions.
  • N-terminus (the death effector domain) of FADD.
  • Cultures of HeLa cells transfected with either the clone encoding the shortened form of FLP or the clone encoding FADD contained at least 60% apoptosis cells, whereas less than 20% ofthe cells in cultures transfected with clones encoding DN-FADD, full-length FLP, FADD and DN-FADD, partial FLP and DN-FADD, or pGFP alone were apoptotic.
  • the C-terminal portion of FLP, encoded by the smaller 2.5 kb FIP mRNA induces apoptosis.
  • MOLECULE TYPE cDNA
  • HYPOTHETICAL NO
  • ANTI-SENSE NO

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

Abstract

L'invention concerne un nouveau gène codant une protéine humaine interagissant avec FADD (FIP). La protéine FIP, qui interagit physiquement avec FADD, est associée à la voie de l'apoptose humaine. La transfection de FIP dans des cellules humaines provoque l'apoptose. La protéine et les séquences codantes FIP peuvent être utilisées dans le traitement de maladies caractérisées par des déficiences au niveau de la régulation de la prolifération cellulaire ainsi que pour le criblage de médicaments influant sur la voie de l'apoptose.
PCT/US1998/013320 1997-06-26 1998-06-26 Proteine humaine interagissant avec fadd (fip) WO1999000499A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU79886/98A AU7988698A (en) 1997-06-26 1998-06-26 Human fadd-interacting protein (fip)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US5079297P 1997-06-26 1997-06-26
US60/050,792 1997-06-26
US8788698P 1998-06-03 1998-06-03
US60/087,886 1998-06-03

Publications (1)

Publication Number Publication Date
WO1999000499A1 true WO1999000499A1 (fr) 1999-01-07

Family

ID=26728679

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1998/013320 WO1999000499A1 (fr) 1997-06-26 1998-06-26 Proteine humaine interagissant avec fadd (fip)

Country Status (2)

Country Link
AU (1) AU7988698A (fr)
WO (1) WO1999000499A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001004153A1 (fr) * 1999-07-12 2001-01-18 Imagene Co., Ltd. Domaine effecteur de mort du mediateur de l'apoptose mammifere, fadd, provoquant la mort des cellules bacteriennes

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996018641A1 (fr) * 1994-12-15 1996-06-20 Yeda Research And Development Co. Ltd. Modulateurs de la fonction des recepteurs de fas/ap01
WO1996025941A1 (fr) * 1995-02-22 1996-08-29 Yeda Research And Development Co. Ltd. Modulateurs de proteines regulatoires
WO1996031603A2 (fr) * 1995-04-03 1996-10-10 The Regents Of The University Of Michigan Procedes et compositions pour reguler le niveau de la proteine 'fadd'

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996018641A1 (fr) * 1994-12-15 1996-06-20 Yeda Research And Development Co. Ltd. Modulateurs de la fonction des recepteurs de fas/ap01
WO1996025941A1 (fr) * 1995-02-22 1996-08-29 Yeda Research And Development Co. Ltd. Modulateurs de proteines regulatoires
WO1996031603A2 (fr) * 1995-04-03 1996-10-10 The Regents Of The University Of Michigan Procedes et compositions pour reguler le niveau de la proteine 'fadd'

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
BOLDIN M P ET AL: "INVOLVEMENT OF MACH, A NOVEL MORT1/FADD-INTERACTING PROTEASE, IN FAS/APO-1- AND TNF RECEPTOR-INDUCED CELL DEATH", CELL, vol. 85, no. 6, 14 June 1996 (1996-06-14), US, pages 803 - 815, XP002037501 *
CHINNAIYAN A M ET AL: "FADD/MORT1 IS A COMMON MEDIATOR OF CD95 (FAS/APO-1) AND TUMOR NECROSIS FACTOR RECEPTOR-INDUCED APOPTOSIS", JOURNAL OF BIOLOGICAL CHEMISTRY. (MICROFILMS), vol. 271, no. 9, 1 March 1996 (1996-03-01), BALTIMORE US, pages 4961 - 4965, XP002047504 *
LI Y ET AL: "INTERACTION OF AN ADENOVIRUS 14.7 KILODALTON PROTEIN INHIBITOR OF TUMOR NECROSIS FACTOR ALPHA CYTOLYSIS WITH A NEW MEMBER OF THE GTPASE SUPERFAMILY OF SIGNAL TRANSDUCERS", JOURNAL OF VIROLOGY., vol. 71, no. 2, February 1997 (1997-02-01), US, pages 1576 - 1582, XP002085584 *
MUZIO M ET AL: "FLICE, A NOVEL FADD-HOMOLOGOUS ICE/CED-3-LIKE PROTEASE, IS RECRUITED TO THE CD95 (FAS/APO-1) DEATH-INDUCING SIGNALING COMPLEX", CELL, vol. 85, no. 6, 14 June 1996 (1996-06-14), US, pages 817 - 827, XP002037500 *
NAGASE T ET AL: "PREDICTION OF THE CODING SEQUENCES OF UNIDENTIFIED HUMAN GENES VI.THE CODING SEQUENCES OF 80 NEW GENES (KIAA0201-KIAA0280) DEDUCED BY ANALYSIS OF CDNA CLONES FROM CELL LINE KG-1 AND BRAIN", DNA RESEARCH, vol. 3, no. 5, 31 October 1996 (1996-10-31), pages 321 - 329, XP002061644 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001004153A1 (fr) * 1999-07-12 2001-01-18 Imagene Co., Ltd. Domaine effecteur de mort du mediateur de l'apoptose mammifere, fadd, provoquant la mort des cellules bacteriennes

Also Published As

Publication number Publication date
AU7988698A (en) 1999-01-19

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