EP 1097226 A1 20010509 - USURPIN, A MAMMALIAN DED-CASPASE HOMOLOGUE THAT PRECLUDES CASPASE-8 RECRUITMENT AND ACTIVATION BY THE CD-95 (FAS, APO-1) RECEPTOR COMPLEX
Title (en)
USURPIN, A MAMMALIAN DED-CASPASE HOMOLOGUE THAT PRECLUDES CASPASE-8 RECRUITMENT AND ACTIVATION BY THE CD-95 (FAS, APO-1) RECEPTOR COMPLEX
Title (de)
USURPIN, SÄUGERTIER DED-CASPASE HOMOLOGES, DAS DIE AKTIVIERUNG DER CASPASE-8 BEIM CD-95 (FAS, APO-1) REZEPTOR INHIBIERT
Title (fr)
L'USURPINE, HOMOLOGUE MAMMIFERE DE LA DED-CASPASE, EMPECHANT LE RECRUTEMENT DE LA CASPASE-8 ET L'ACTIVATION DE CELLE-CI PAR LE COMPLEXE DU RECEPTEUR DE CD-95 (FAS, APO-1)
Publication
Application
Priority
- CA 9900615 W 19990707
- US 9200598 P 19980708
Abstract (en)
[origin: WO0003023A1] The protein Usurpin, an endogenous mammalian regulator of the process of apoptotic cell suicide, is provided. Provided are three Usurpin proteins having an amino acid sequence selected from the group consisting of: SEQ.ID.NO.:4, SEQ.ID.NO.:5, and SEQ.ID.NO.:6 that arise from alternative splicing of the Usurpin gene. The full-length Usurpin polypeptide (Usurpin- alpha ) has features in common with pro-caspase-8 and -10, including tandem "death effector domains" (DEDs) on the N-terminus and a large subunit/small subunit caspase-like domain, but it lacks key residues that are necessary for caspase proteolytic activity. However, Usurpin heterodimerizes with pro-caspase-8 and precludes pro-caspase-8 recruitment by the FADD/MORT1 adapter protein, thus blocking an important interaction in the CD95 (Fas/APO-1) apoptotic process. Therefore, Usurpin is useful as a modulator of the sensitivity of cells to CD95 (Fas/APO-1)-mediated apoptosis. Accordingly, the present invention also provides methods of modulating apoptosis by introducing Usurpin polypeptides into cells. Also provided are various purified nucleotide sequences encoding Usurpin. Also provided are methods of identifying inhibitors of the interaction between Usurpin and pro-caspase-8. Such inhibitors will be useful in controlling the interaction between Usurpin and pro-caspase-8, thus modulating apoptosis.
IPC 1-7
C12N 15/57; C12N 5/10; C12N 1/21; C12N 9/64; C07K 16/40; G01N 33/50
IPC 8 full level
C07K 14/47 (2006.01); C07K 16/18 (2006.01); C12N 1/15 (2006.01); C12N 1/19 (2006.01); C12N 1/21 (2006.01); C12N 5/10 (2006.01); C12N 9/64 (2006.01); C12N 15/09 (2006.01); C12N 15/57 (2006.01); C12Q 1/02 (2006.01); G01N 33/50 (2006.01)
CPC (source: EP)
C12N 9/6475 (2013.01)
Citation (search report)
See references of WO 0003023A1
Designated contracting state (EPC)
AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE
DOCDB simple family (publication)
WO 0003023 A1 20000120; CA 2332346 A1 20000120; EP 1097226 A1 20010509; JP 2002520025 A 20020709
DOCDB simple family (application)
CA 9900615 W 19990707; CA 2332346 A 19990707; EP 99927635 A 19990707; JP 2000559244 A 19990707