DOBI is cleaved by caspases during TRAIL-induced apoptotic cell death.
Downstream of Bid (DOBI) known as Pus10, has been identified as a modulator of TRAIL-induced cell death using RNAi library screening. The crystal structure of DOBI has revealed that it is a crescent-shaped protein containing the pseudouridine synthase catalytic domain and a THUMP-containing domain. Here, we demonstrated that DOBI is expressed in various tissues such as heart and lung, and is also expressed in various tumor cells such as HeLa and A549. Although ectopic expression of DOBI does not promote TRAIL death signaling in HeLa cells, knock-down of DOBI expression using shRNA inhibited TRAIL death signaling. DOBI is cleaved into a 54 kD cleaved DOBI during cell death, and the recombinant DOBI protein can be directly cleaved by caspases-3, or -8 in vitro. Together, these data suggest that the cleaved DOBI may acquire a new function, possibly by cooperating with tBid in the mitochondrial event of cell death caused by TRAIL.
Park
Sun-Young
SY
Department of Biochemistry & Molecular Biology, Chosun University School of Medicine, Gwang-Ju 501-759, Korea.
Shin
Jin Na
JN
Woo
Ha Na
HN
Piya
Sujan
S
Moon
Ae Ran
AR
Seo
Young-Woo
YW
Seol
Dai-Wu
DW
Kim
Tae-Hyoung
TH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D006836:Hydro-Lyases / Q000378:metabolism*; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D011994:Recombinant Proteins / Q000494:pharmacology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D014162:Transfection
D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; D020169:Caspases; D006836:Hydro-Lyases; C022479:pseudouridylate synthetase