J Biol Chem. 1997 Aug 8;272(32):19641-4.

CASH, a novel caspase homologue with death effector domains.External

Goltsev, Y. V., Kovalenko, A. V., Arnold, E., Varfolomeev, E. E., Brodianskii, V. M., Wallach, D.,
--- - Department of Membrane Research and Biophysics, Weizmann Institute of Science, 76100 Rehovot, Israel.
CASP-8 and CASP-10, members of a cysteine protease family that participates in apoptosis, interact with MORT1/FADD, an adapter protein in the CD120a (p55 tumor necrosis factor receptor), and CD95 (Fas/Apo-1) death-inducing signaling pathways, through a shared N-terminal sequence motif, the death effector domain. We report cloning of two splice variants of a novel protein, CASH, that contain two N-terminal death effector domains and can bind through them to each other, to MORT1/FADD, to CASP-8, and to CASP-10. The unique C-terminal part of the longer variant shows marked sequence homology to the caspase protease region yet lacks several of the conserved caspase active site residues, suggesting that it is devoid of cysteine protease activity. Overexpression of the short CASH splice variant strongly inhibited cytotoxicity induction by CD120a and CD95. Expression of the longer variant, while inhibiting cytotoxicity in HeLa cells, had a marked cytocidal effect in 293 cells that could be shown to involve its protease homology region. The findings suggest that CASH acts as an attenuator and/or initiator in CD95 and CD120a signaling for cell death.
PMID: 9289491External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vitro interaction
  DD1 DD2 Reference
Family DD1 DD2 Method Species Region Expression Species Region Expression
DED Caspase8 Link FLIP Yeast two-hybrid Not specified Not specified Yeast Human Full length Yeast 9289491
DED FADD Link FLIP Yeast two-hybrid Not specified Not specified Yeast Human Full length Yeast 9289491
DED FLIP Link FLIP Yeast two-hybrid Human Full length Yeast Human Full length Yeast 9289491
(Link: click this icon to show interactions only between the two corresponding DDs)