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O‐GlcNAcase is Cleaved Between Its Glycosidase & Histone Acetyltransferase Domains by Caspase‐3 During Apoptosis
Author(s) -
Butkinaree Chutikarn,
Cheung Win D.,
Park Kyoungsook,
Hart Gerald W.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a257-a
Subject(s) - microbiology and biotechnology , cleavage (geology) , cleavage stimulation factor , cleavage factor , apoptosis , caspase 2 , transcription factor , caspase 3 , caspase , chemistry , biology , biochemistry , programmed cell death , gene , messenger rna , paleontology , fracture (geology)
O‐GlcNAc is a dynamic post‐translational modification on many nucleocytoplasmic proteins, ranging from transcription factors, signaling proteins, to cytoskeletal proteins. O‐GlcNAc is a nutrient sensor involved in the regulation of cellular activity, including transcription, response to stress, and protein‐protein interactions. Recent studies have shown that O‐GlcNAc cycling is affected by apoptosis induction. O‐GlcNAcase, the O‐GlcNAc removal enzyme, has been shown to be a substrate of caspase‐3 in vitro. Here we identify the cleavage site of O‐GlcNAcase by caspase‐3 using Edman sequencing. A point mutation at the cleavage site abrogates cleavage by caspase‐3 in vitro. We also show that O‐GlcNAcase is a substrate of caspase‐3 during Fas‐mediated apoptosis in vivo in various cell lines separating the two functional domains of this bi‐functional enzyme. Interestingly, caspase‐3 cleavage does not affect the activity of the enzyme nor its localization. We are currently investigating how O‐GlcNAcase cleavage by caspase‐3 is involved in the apoptotic events using the mutant lacking a caspase‐3 cleavage site during apoptotic induction. These data will give a better understanding of how O‐GlcNAc and O‐GlcNAcase are involved in the regulation of apoptosis. Supported by NIH grants CA42486 and HD13563 and G.W. H. receives a share of royalty received by the university on sales of the CTD 110.6 antibody. The terms of this arrangement are being managed by The Johns Hopkins University in accordance with its conflict of interest policies.