[go: up one dir, main page]

WO2000077168A3 - ANTAGONISTES DES VOIES DE SIGNALISATION BMP ET TGF$g(b) - Google Patents

ANTAGONISTES DES VOIES DE SIGNALISATION BMP ET TGF$g(b) Download PDF

Info

Publication number
WO2000077168A3
WO2000077168A3 PCT/US2000/016250 US0016250W WO0077168A3 WO 2000077168 A3 WO2000077168 A3 WO 2000077168A3 US 0016250 W US0016250 W US 0016250W WO 0077168 A3 WO0077168 A3 WO 0077168A3
Authority
WO
WIPO (PCT)
Prior art keywords
smurf1
bmp
tgfβ
signalling
smurf2
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/US2000/016250
Other languages
English (en)
Other versions
WO2000077168A2 (fr
Inventor
Gerald H Thomsen
Jeffrey Wrana
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.)
HSC Research and Development LP
Research Foundation of the State University of New York
Original Assignee
HSC Research and Development LP
Research Foundation of the State University of New York
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 HSC Research and Development LP, Research Foundation of the State University of New York filed Critical HSC Research and Development LP
Priority to IL14700500A priority Critical patent/IL147005A0/xx
Priority to CA002376675A priority patent/CA2376675A1/fr
Priority to JP2001504003A priority patent/JP2003502064A/ja
Priority to EP00941398A priority patent/EP1192174A4/fr
Priority to AU56107/00A priority patent/AU782355B2/en
Priority to US10/009,945 priority patent/US7354722B1/en
Publication of WO2000077168A2 publication Critical patent/WO2000077168A2/fr
Publication of WO2000077168A3 publication Critical patent/WO2000077168A3/fr
Anticipated expiration legal-status Critical
Priority to AU2005225080A priority patent/AU2005225080B2/en
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/93—Ligases (6)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Zoology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Biomedical Technology (AREA)
  • Wood Science & Technology (AREA)
  • Genetics & Genomics (AREA)
  • Rheumatology (AREA)
  • General Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Microbiology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Neurosurgery (AREA)
  • Biochemistry (AREA)
  • Neurology (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

L'invention concerne des éléments uniques de la famille Hect des ubiquitine ligases qui ciblent spécifiquement des protéines Smad spécifiques des voies de signalisation BMP et TGFβ/activine. Les nouvelles ligases ont été appelées Smurf1 et Smurf2. Elles interagissent directement avec les protéines Smad1 et 5 et avec Smad7, respectivement, et régulent l'ubiquitination, le renouvellement et l'activité de protéines Smad et d'autres protéines de ces voies de signalisation. Smurf1 intervient dans les réponses biologiques à BMP, mais pas dans la signalisation d'activine. Dans des embryons d'amphibiens, Smurf1 inhibe les signaux de BMP endogène, ce qui entraîne une formation de motif et une spécification de destin cellulaire modifiées dans le mésoderme et l'ectoderme. La présente invention concerne un lien régulatoire unique entre la voie d'ubiquitination et la régulation de la détermination du destin cellulaire par la superfamille des TGFβ au cours du développement embryonnaire. De ce fait, Smurf1 constitue un régulateur négatif de la transduction de signal Smad1 : en ciblant Smad1, Smurf1 bloque la signalisation BMP. Dans des cellules de mammifère, Smurf2 supprime la signalisation TGFβ, et, chez le xénope, bloque la formation de mésoderme dorsal et provoque une troncature antérieure des embryons. Smurf2 forme un complexe stable avec Smad7, ce qui entraîne une dégradation et une diminution de la signalisation TGFβ/activine.
PCT/US2000/016250 1999-06-11 2000-06-12 ANTAGONISTES DES VOIES DE SIGNALISATION BMP ET TGF$g(b) Ceased WO2000077168A2 (fr)

Priority Applications (7)

Application Number Priority Date Filing Date Title
IL14700500A IL147005A0 (en) 1999-06-11 2000-06-12 Antagonists of bmp and tgfb signaling pathways
CA002376675A CA2376675A1 (fr) 1999-06-11 2000-06-12 Antagonistes des voies de signalisation bmp et tgf.beta.
JP2001504003A JP2003502064A (ja) 1999-06-11 2000-06-12 ＢＭＰおよびＴＧＦβシグナル伝達経路のアンタゴニスト
EP00941398A EP1192174A4 (fr) 1999-06-11 2000-06-12 Antagonistes des voies de signalisation bmp et tgf beta
AU56107/00A AU782355B2 (en) 1999-06-11 2000-06-12 Antagonists of BMP and TGFbeta signalling pathways
US10/009,945 US7354722B1 (en) 1999-06-11 2000-06-12 Modulators of Smurf and BMP/TGFβ signaling pathways
AU2005225080A AU2005225080B2 (en) 1999-06-11 2005-10-20 Antagonists of BMP and TGFBeta signalling pathways

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US13896999P 1999-06-11 1999-06-11
US60/138,969 1999-06-11

Publications (2)

Publication Number Publication Date
WO2000077168A2 WO2000077168A2 (fr) 2000-12-21
WO2000077168A3 true WO2000077168A3 (fr) 2001-05-03

Family

ID=22484504

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2000/016250 Ceased WO2000077168A2 (fr) 1999-06-11 2000-06-12 ANTAGONISTES DES VOIES DE SIGNALISATION BMP ET TGF$g(b)

Country Status (7)

Country Link
EP (1) EP1192174A4 (fr)
JP (1) JP2003502064A (fr)
CN (1) CN100379752C (fr)
AU (1) AU782355B2 (fr)
CA (1) CA2376675A1 (fr)
IL (1) IL147005A0 (fr)
WO (1) WO2000077168A2 (fr)

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7358056B1 (en) 1999-08-30 2008-04-15 Signal Pharmaceuticals Methods for modulating signal transduction mediated by TGF-β and related proteins
US20030092603A1 (en) * 2001-10-09 2003-05-15 Mundy Gregory R. Identification of specific modulators of bone formation
EP1639008A1 (fr) * 2003-07-01 2006-03-29 VIB vzw Tnf recepteur 2 ubiquitine et ses utilisations
KR101242260B1 (ko) * 2003-09-11 2013-03-13 휴비트 제노믹스 가부시키가이샤 경화를 초래하는 증식성 질환의 검출방법 및 키트, 경화를초래하는 증식성 질환의 예방 및/또는 치료제, 그리고경화를 초래하는 증식성 질환의 예방 및/또는 치료에유효한 물질을 동정하는 방법 및 키트
GB0526664D0 (en) * 2005-11-30 2006-02-08 Plasticell Ltd Method
US8898056B2 (en) 2006-03-01 2014-11-25 Qualcomm Incorporated System and method for generating a separated signal by reordering frequency components
JP2010519274A (ja) 2007-02-21 2010-06-03 フラームス・インテルウニフェルシタイル・インステイチュート・フォール・ビオテヒノロヒー・ヴェーゼットウェー（ヴェーイーベー・ヴェーゼットウェー） ＴＮＦおよびα−ガラクトシルセラミドを使用する併用療法
CA2688299A1 (fr) 2007-05-29 2008-12-18 President And Fellows Of Harvard College Molecules impliquees dans la regulation de l'activite des osteoblastes et des osteoclastes, et leurs methodes d'utilisation
US9745589B2 (en) 2010-01-14 2017-08-29 Cornell University Methods for modulating skeletal remodeling and patterning by modulating SHN2 activity, SHN3 activity, or SHN2 and SHN3 activity in combination
US9403810B2 (en) * 2014-05-14 2016-08-02 Novartis Ag Carboxamide derivatives
TW201623288A (zh) * 2014-05-14 2016-07-01 諾華公司 甲醯胺衍生物
KR102360028B1 (ko) * 2014-12-26 2022-02-08 삼성전자주식회사 Smurf2의 저해제를 포함하는 세포 또는 개체의 노화를 감소시키기 위한 조성물 및 그의 용도
CN110196326A (zh) * 2019-06-05 2019-09-03 武汉合研生物医药科技有限公司 一种TGFβR1（T204D）酶活性的快速检测方法及其应用
CN110592032B (zh) * 2019-10-14 2021-04-13 北京理工大学 泛素连接酶Smurf1突变体、编码基因及用途
US12098384B2 (en) 2021-01-21 2024-09-24 Cellid Co., Ltd. Adenoviral vector not including replication competent adenovirus, and use thereof
CN117721131A (zh) * 2023-12-19 2024-03-19 吉林大学 一种重组骨形态发生蛋白突变体的制备方法和应用
CN119386159B (zh) * 2024-12-31 2025-04-22 温州医科大学 一种mRNA-多肽复合物及其制备方法和应用

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6087122A (en) * 1998-02-05 2000-07-11 Zeneca Limited Human E3 ubiquitin protein ligase
US6103869A (en) * 1997-05-20 2000-08-15 Ludwig Institute For Cancer Research Smad2 phosphorylation and interaction with Smad4

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6001619A (en) * 1995-10-04 1999-12-14 Cold Spring Harbor Laboratory Ubiquitin ligases, and uses related thereto

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6103869A (en) * 1997-05-20 2000-08-15 Ludwig Institute For Cancer Research Smad2 phosphorylation and interaction with Smad4
US6087122A (en) * 1998-02-05 2000-07-11 Zeneca Limited Human E3 ubiquitin protein ligase

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
PERSSON ET AL.: "Transforming growth factor (TGF-beta)-specific signaling by chimeric TGF-beta type II receptor with intracellular domain of activin type IIB receptor", THE JOURNAL OF BIOLOGY CHEMISTRY, vol. 272, no. 34, 22 August 1997 (1997-08-22), pages 21187 - 21194, XP002934435 *
WRANA ET AL.: "The smad pathway", CYTOKINE AND GROWTH FACTOR REVIEWS, vol. 11, 2000, pages 5 - 13, XP002934436 *
ZHU ET AL.: "A SMAD ubiguitin ligase targets the BMP pathway and affects embryonic pattern formation", NATURE, vol. 400, 12 August 1999 (1999-08-12), pages 687 - 693, XP002934434 *

Also Published As

Publication number Publication date
AU5610700A (en) 2001-01-02
CN100379752C (zh) 2008-04-09
EP1192174A2 (fr) 2002-04-03
JP2003502064A (ja) 2003-01-21
IL147005A0 (en) 2002-08-14
AU782355B2 (en) 2005-07-21
WO2000077168A2 (fr) 2000-12-21
CA2376675A1 (fr) 2000-12-21
CN1409722A (zh) 2003-04-09
EP1192174A4 (fr) 2002-08-28

Similar Documents

Publication Publication Date Title
WO2000077168A3 (fr) ANTAGONISTES DES VOIES DE SIGNALISATION BMP ET TGF$g(b)
Zhao et al. Smurf1 inhibits osteoblast differentiation and bone formation in vitro and in vivo
Shirakabe et al. Roles of Meltrin β/ADAM19 in the processing of neuregulin
Coyle-Rink et al. Developmental expression of Wnt signaling factors in mouse brain
Alexander et al. Stromelysin-1 regulates adipogenesis during mammary gland involution
Allen et al. Hedgehog signaling regulates sebaceous gland development
Borgs et al. Period 2 regulates neural stem/progenitor cell proliferation in the adult hippocampus
Yamamura et al. A heart segmental defect in the anterior-posterior axis of a transgenic mutant mouse
Campbell et al. Annexin A6 interacts with p65 and stimulates NF‐κB activity and catabolic events in articular chondrocytes
Ito et al. Receptor‐regulated and inhibitory Smads are critical in regulating transforming growth factorβ–mediated Meckel's cartilage development
Yavari et al. Human metalloprotease-disintegrin Kuzbanian regulates sympathoadrenal cell fate in development and neoplasia
Su et al. The evolutionally conserved activity of Dapper2 in antagonizing TGF‐ß signaling
Gorski et al. Skeletal‐specific expression of Fgd1 during bone formation and skeletal defects in faciogenital dysplasia (FGDY; Aarskog syndrome)
Selvamurugan et al. Overexpression of Runx2 directed by the matrix metalloproteinase‐13 promoter containing the AP‐1 and Runx/RD/Cbfa sites alters bone remodeling in vivo
Blanchette et al. Involvement of Smads in TGFβ1‐induced furin (fur) transcription
Kablar et al. Invited Reviews-Skeletal muscle development in the mouse embryo
Hosokawa et al. Epithelial‐specific requirement of FGFR2 signaling during tooth and palate development
Lamoreux et al. The pinkeyed‐dilution protein and the eumelanin/pheomelanin switch: In support of a unifying hypothesis
Walker et al. Shades of meaning: the pigment‐type switching system as a tool for discovery
Bischof et al. Effects of decidua-conditioned medium and insulin-like growth factor binding protein-1 on trophoblastic matrix metalloproteinases and their inhibitors
US5585087A (en) Assay for identifying extracellular signaling proteins
Muraoka et al. Mesenchymal expression of nuclear factor-κB inhibits epithelial growth and branching in the embryonic chick lung
St John et al. Expression of galectin-1 in the olfactory nerve pathway of rat
Das et al. Drosophila dSmad2 and Atr‐I transmit activin/TGFβ signals
Miskin et al. αMUPA mice: a transgenic model for longevity induced by caloric restriction

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ DE DK DM EE ES FI GB GD GE HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
AK Designated states

Kind code of ref document: A3

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ DE DK DM EE ES FI GB GD GE HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A3

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
ENP Entry into the national phase

Ref document number: 2376675

Country of ref document: CA

Ref country code: CA

Ref document number: 2376675

Kind code of ref document: A

Format of ref document f/p: F

ENP Entry into the national phase

Ref country code: JP

Ref document number: 2001 504003

Kind code of ref document: A

Format of ref document f/p: F

WWE Wipo information: entry into national phase

Ref document number: 56107/00

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: 2000941398

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 008113548

Country of ref document: CN

WWP Wipo information: published in national office

Ref document number: 2000941398

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWG Wipo information: grant in national office

Ref document number: 56107/00

Country of ref document: AU