RIP: A novel protein containing a death domain that interacts with Fas/APO-1 (CD95) in yeast and causes cell death

Ben Z. Stanger, Philip Leder, Tae Ho Lee, Emily Kim, Brian Seed

Research output: Contribution to journalArticlepeer-review

813 Citations (Scopus)

Abstract

Ligation of the extracellular domain of the cell surface receptor Fas/APO-1 (CD95) elicits a characteristic programmed death response in susceptible cells. Using a genetic selection based on protein-protein interaction in yeast, we have identified two gene products that associate with the intracellular domain of Fas: Fas itself, and a novel 74 kDa protein we have named RIP, for receptor interacting protein. RIP also interacts weakly with the p55 tumor necrosis factor receptor (TNFRI) intracellular domain, but not with a mutant version of Fas corresponding to the murine Iprocg mutation. RIP contains an N-terminal region with homology to protein kinases and a C-terminal region containing a cytoplasmic motif (death domain) present in the Fas and TNFR1 intracellular domains. Transient over-expression of RIP causes transfected cells to undergo the morphological changes characteristic of apoptosis. Taken together, these properties indicate that RIP is a novel form of apoptosis-inducing protein.

Original languageEnglish
Pages (from-to)513-523
Number of pages11
JournalCell
Volume81
Issue number4
DOIs
Publication statusPublished - 1995 May 19

Bibliographical note

Funding Information:
We are grateful to Roger Brent and Jeno Gyuris for their generous contributions of reagents and support throughout this work and Walde-mar Kolanus for his assistance in setting up and carrying out the yeast screen. We thank Jon Madison for help with the yeast P-gal assay and Connie Cepko for use of the BAG vector. We appreciate the generous assistance of Frank McKeon and his laboratory in performing transfections. In addition, we thank Yasumasa Ishida, David Chan, Tim Lane, Michelle Kelliher, and other members of the Leder lab for discussions and advice, as well as Nancy Chiu and Felipe PimenteCMuinos in the Seed lab for experimental assistance. This work was supported in part by National Institutes of Health grant DK43031. B. 2. S. is a predoctoral fellow of the Howard Hughes Medical Institute.

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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