title: Genome-wide screening and identification of novel proteolytic cleavage targets of caspase-8 and -10 in vitro.
abstract: Apoptosis executed by the mammalian caspase family plays a fundamental role in cellular homeostasis. Deregulation of this process is associated with several human diseases. The multimerization of ligand-induced death receptors results in the recruitment of the death inducing signaling complex and autocatalytic activation of initiator caspases, including caspase-8 and -10. However, it is still unclear how initiator caspases trigger and control the early apoptotic signaling pathways, partly because the downstream proteolytic cleavage targets of the initiator caspases are not completely known. Although it is known that a number of proteins are cleaved by various members of the caspase family, the identification of specific cleavage substrates of the initiator caspases 8 and 10, has been hindered by a lack of systematic and broadly applicable strategies for substrate identification. In the present study we constructed a mouse cDNA library and used it to perform a systematic, genome-wide screen for novel in vitro substrates of caspase-8 and -10. From this, we successfully identified six putative caspase substrates, including five novel proteins (ABCF1, AKAP1, CPE, DOPEY1 and GOPC1) that may be targeted specifically by the initiator caspases 8 and 10 during the early stages of apoptosis. These findings may provide useful information for elucidating the apoptotic signaling pathways downstream of the death receptors.
authors.affiliation: Functional Genoproteome Research Centre, Konkuk University, Seoul 143-701, Korea.
authors.forename: Seunghee
authors.initials: S
authors.lastname: Bae
authors.forename: Tae-Su
authors.initials: TS
authors.lastname: Ha
authors.forename: Youngmin
authors.initials: Y
authors.lastname: Yoon
authors.forename: Joonyoung
authors.initials: J
authors.lastname: Lee
authors.forename: Hwa Jun
authors.initials: HJ
authors.lastname: Cha
authors.forename: Hoesook
authors.initials: H
authors.lastname: Yoo
authors.forename: Tae-Boo
authors.initials: TB
authors.lastname: Choe
authors.forename: Shunhua
authors.initials: S
authors.lastname: Li
authors.forename: Insook
authors.initials: I
authors.lastname: Sohn
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Cha-Soon
authors.initials: CS
authors.lastname: Kim
authors.forename: Hyeon-Ok
authors.initials: HO
authors.lastname: Jin
authors.forename: Hyung-Chahn
authors.initials: HC
authors.lastname: Lee
authors.forename: In-Chul
authors.initials: IC
authors.lastname: Park
authors.forename: Chong Soon
authors.initials: CS
authors.lastname: Kim
authors.forename: Young-Woo
authors.initials: YW
authors.lastname: Jin
authors.forename: Sung K
authors.initials: SK
authors.lastname: Ahn
mesh_terms: D000818:Animals; D053455:Caspase 10 / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism*; D002999:Clone Cells; D019295:Computational Biology; D018076:DNA, Complementary / Q000302:isolation & purification; D015723:Gene Library; D016678:Genome / Q000235:genetics*; D008099:Liver / Q000201:enzymology; D051379:Mice; D011499:Protein Processing, Post-Translational; D015203:Reproducibility of Results; D013379:Substrate Specificity
chemical_list: D018076:DNA, Complementary; D053455:Caspase 10; D053181:Caspase 8