Title:
A METHOD OF MODULATING THE EFFICIENCY OF TRANSLATION TERMINATION AND DEGRADATION OF ABERRANT MRNA INVOLVING A SURVEILLANCE COMPLEX COMPRISING HUMAN UPF1P, EUCARYOTIC RELEASE FACTOR 1 AND EUCARYOTIC RELEASE FACTOR 3
Document Type and Number:
WIPO Patent Application WO1999061600
Kind Code:
A3
Abstract:
This invention provides a method of modulating translation termination efficiency of mRNA and/or promoting degradation of aberrant transcripts. Also, this invention provides a method of screening for a drug active involved in enhancing translation termination and a method for identifying a disease state involving defective the protein complex. This invention provides a purified complex comprising an amount of a human Upflp protein, a peptidyl eucaryotic release factor 1 (eRF1) and a peptidyl eucaryotic release factor 3 (eRF3) effective to modulate translation termination. Further, this invention provides an expression vector which comprises a nucleic acid encoding a human Upflp protein, a peptidyl eucaryotic release factor 1 (eRF1) and a peptidyl eucaryotic release factor 3 (eRF3) operably linked to a regulatory element. This invention provides an antibody which binds to the complex comprising an amount of a human Upflp protein, a peptidyl eucaryotic release factor 1 (eRF1) and a peptidyl eucaryotic release factor 3 (eRF3)effective to modulate translation termination. This invention provides an agent which inhibits or modulates the binding of human Upflp to eRF1 or eRF3. The agent may inhibit or facilitate the binding of human Upflp to eRF1 or eRF3.
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Inventors:
PELTZ STUART (US)
CZAPLINSKI KEVIN (US)
WENG YOUMIN (US)
CZAPLINSKI KEVIN (US)
WENG YOUMIN (US)
Application Number:
PCT/US1999/011826
Publication Date:
February 10, 2000
Filing Date:
May 27, 1999
Export Citation:
Assignee:
UNIV NEW JERSEY MED (US)
PELTZ STUART (US)
CZAPLINSKI KEVIN (US)
WENG YOUMIN (US)
PELTZ STUART (US)
CZAPLINSKI KEVIN (US)
WENG YOUMIN (US)
International Classes:
A61K31/7105; A61K38/00; A61K38/17; A61K39/395; A61K45/00; A61P3/06; A61P7/00; G01N33/50; A61P13/12; A61P27/02; A61P35/00; A61P43/00; C07K14/47; C07K16/18; C12N9/00; C12N15/09; C12P21/08; C12Q1/48; C12Q1/68; G01N33/15; (IPC1-7): C12N9/00; C12N15/11; C07K14/47; C07K16/40; C12Q1/68; C12Q1/48; A61K38/17
Domestic Patent References:
| WO1997012617A1 | 1997-04-10 | |||
| WO1996022301A1 | 1996-07-25 |
Other References:
WENG Y ET AL: "GENETIC AND BIOCHEMICAL CHARACTERIZATION OF MUTATIONS IN THE ATPASE AND HELICASE REGIONS OF THE UPF1 PROTEIN", MOLECULAR AND CELLULAR BIOLOGY, vol. 16, no. 10, 1 October 1996 (1996-10-01), pages 5477 - 5490, XP000616496, ISSN: 0270-7306
CZAPLINSKI, K. ET AL.: "The surveillance complex interacts with the translation release factors to enhance termination and degrade aberrant mRNAs", GENES AND DEVELOPMENT, vol. 12, no. 11, 1 June 1998 (1998-06-01), pages 1665 - 1677, XP002119661
PELTZ S W ET AL: "NONSENSE-MEDIATED MRNA DECAY IN YEAST", PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY, vol. 47, 1 January 1994 (1994-01-01), pages 271 - 298, XP000617057, ISSN: 0079-6603
DATABASE MEDLINE [online] 16 December 1996 (1996-12-16), ANDJELKOVIC ET AL.: "The catalytic subunit of protein phosphatase 2 aassociates with the translation termination factor eRF1", XP002033498, retrieved from MEDLIN accession no. 2191
CZAPLINSKI, K. ET AL.: "The surveillance complex interacts with the translation release factors to enhance termination and degrade aberrant mRNAs", GENES AND DEVELOPMENT, vol. 12, no. 11, 1 June 1998 (1998-06-01), pages 1665 - 1677, XP002119661
PELTZ S W ET AL: "NONSENSE-MEDIATED MRNA DECAY IN YEAST", PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY, vol. 47, 1 January 1994 (1994-01-01), pages 271 - 298, XP000617057, ISSN: 0079-6603
DATABASE MEDLINE [online] 16 December 1996 (1996-12-16), ANDJELKOVIC ET AL.: "The catalytic subunit of protein phosphatase 2 aassociates with the translation termination factor eRF1", XP002033498, retrieved from MEDLIN accession no. 2191
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