PMID- 12724313
OWN - NLM
STAT- MEDLINE
DCOM- 20030818
LR  - 20210206
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 278
IP  - 27
DP  - 2003 Jul 4
TI  - Roles of the tetratricopeptide repeat domain in O-GlcNAc transferase targeting 
      and protein substrate specificity.
PG  - 24608-16
AB  - The abundant and dynamic post-translational modification of nuclear and cytosolic 
      proteins by beta-O-linked N-acetylglucosamine (O-GlcNAc) is catalyzed by 
      O-GlcNAc-transferase (OGT). Recently, we reported the identification of a novel 
      family of OGT-interacting proteins (OIPs) that interact strongly with the 
      tetratricopeptide repeat (TPR) domain of OGT (Iyer, S. P., Akimoto, Y., and Hart, 
      G. W. (2003) J. Biol. Chem. 278, 5399-5409). Members of this family are modified 
      by O-GlcNAc and are excellent substrates of OGT. Here, we further investigated 
      the role of the TPR domain in the O-GlcNAcylation of OIP106, one of the members 
      of this OIP family. Using N-terminal deletions, we first identified the region of 
      OIP106 that binds OGT, termed the OGT-interacting domain (OID). Deletion analysis 
      indicated that TPRs 2-6 of OGT interact with the OID of OIP106. The apparent Km 
      of OGT for the OID of OIP106 is 3.35 microm. Unlike small peptide substrates, 
      glycosylation of the OID was dependent upon its interaction with the first 6 TPRs 
      of OGT. Furthermore, the isolated TPR domain of OGT competitively inhibited 
      glycosylation of the OID protein, but did not inhibit glycosylation of a 12-amino 
      acid casein kinase II peptide substrate, providing kinetic evidence for the role 
      of the TPR domain as a protein substrate docking site. Additionally, both the OID 
      of OIP106 and nucleoporin p62 competed with each other for glycosylation by OGT. 
      These studies support the model that the catalytic subunit of OGT achieves both 
      high specificity and a remarkable diversity of substrates by complexing with a 
      variety of targeting proteins via its TPR protein-protein interaction domains.
FAU - Iyer, Sai Prasad N
AU  - Iyer SP
AD  - Department of Biological Chemistry, Johns Hopkins University School of Medicine, 
      Baltimore, Maryland 21205-2185, USA.
FAU - Hart, Gerald W
AU  - Hart GW
LA  - eng
GR  - HD13563/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030430
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - EC 2.4.1.- (N-Acetylglucosaminyltransferases)
RN  - EC 2.4.1.- (O-GlcNAc transferase)
SB  - IM
MH  - Animals
MH  - Catalytic Domain/genetics
MH  - Models, Molecular
MH  - N-Acetylglucosaminyltransferases/*analysis/genetics/metabolism
MH  - Protein Binding
MH  - Rats
MH  - Substrate Specificity/genetics
EDAT- 2003/05/02 05:00
MHDA- 2003/08/19 05:00
CRDT- 2003/05/02 05:00
PHST- 2003/05/02 05:00 [pubmed]
PHST- 2003/08/19 05:00 [medline]
PHST- 2003/05/02 05:00 [entrez]
AID - S0021-9258(20)86915-4 [pii]
AID - 10.1074/jbc.M300036200 [doi]
PST - ppublish
SO  - J Biol Chem. 2003 Jul 4;278(27):24608-16. doi: 10.1074/jbc.M300036200. Epub 2003 
      Apr 30.