PMID- 12519782
OWN - NLM
STAT- MEDLINE
DCOM- 20030502
LR  - 20231213
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 278
IP  - 13
DP  - 2003 Mar 28
TI  - Nuclear receptor coactivator thyroid hormone receptor-binding protein (TRBP) 
      interacts with and stimulates its associated DNA-dependent protein kinase.
PG  - 11471-9
AB  - Nuclear receptors mediate gene activation through ligand-dependent interaction 
      with coactivators. We previously cloned and characterized thyroid hormone 
      receptor-binding protein, TRBP (NcoA6: AIB3/ASC-2/RAP250/PRIP/TRBP/NRC), as an 
      LXXLL-containing coactivator that associates with coactivator complexes through 
      its C terminus. To search for protein factors involved in TRBP action, we 
      identified a distinct set of proteins from HeLa nuclear extract that interacts 
      with the C terminus of TRBP. Analysis by mass spectrometric protein sequencing 
      revealed a DNA-dependent protein kinase (DNA-PK) complex including its catalytic 
      subunit and regulatory subunits, Ku70 and Ku86. DNA-PK is a heterotrimeric 
      nuclear phosphatidylinositol 3-kinase that functions in DNA repair, 
      recombination, and transcriptional regulation. DNA-PK phosphorylates TRBP at its 
      C-terminal region, which directly interacts with Ku70 but not Ku86 in vitro. In 
      addition, in the absence of DNA, TRBP itself activates DNA-PK, and the 
      TRBP-stimulated DNA-PK activity has an altered phosphorylation pattern from 
      DNA-stimulated activity. An anti-TRBP antibody inhibits TRBP-induced kinase 
      activity, suggesting that protein content of TRBP is responsible for the 
      stimulation of DNA-independent kinase activity. Furthermore, in DNA-PK-deficient 
      scid cells, TRBP-mediated transactivation is significantly impaired, and nuclear 
      localization of TRBP is altered. The activation of DNA-PK in the absence of DNA 
      ends by the coactivator TRBP suggests a novel mechanism of coactivator-stimulated 
      DNA-PK phosphorylation in transcriptional regulation.
FAU - Ko, Lan
AU  - Ko L
AD  - Department of Gene Regulation, Bone and Inflammation Research, Lilly Research 
      Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA. 
      kol@lilly.com
FAU - Chin, William W
AU  - Chin WW
LA  - eng
PT  - Journal Article
DEP - 20030107
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Thyroid Hormones)
RN  - EC 2.7.11.1 (DNA-Activated Protein Kinase)
RN  - EC 2.7.11.1 (PRKDC protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Carrier Proteins/*metabolism
MH  - DNA-Activated Protein Kinase
MH  - *DNA-Binding Proteins
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Enzyme Activation
MH  - Fluorescent Antibody Technique
MH  - HeLa Cells
MH  - Humans
MH  - Membrane Proteins/*metabolism
MH  - Nuclear Proteins
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Recombination, Genetic
MH  - Substrate Specificity
MH  - Thyroid Hormones/*metabolism
MH  - Transcription, Genetic
MH  - Thyroid Hormone-Binding Proteins
EDAT- 2003/01/10 04:00
MHDA- 2003/05/03 05:00
CRDT- 2003/01/10 04:00
PHST- 2003/01/10 04:00 [pubmed]
PHST- 2003/05/03 05:00 [medline]
PHST- 2003/01/10 04:00 [entrez]
AID - S0021-9258(19)32435-4 [pii]
AID - 10.1074/jbc.M209723200 [doi]
PST - ppublish
SO  - J Biol Chem. 2003 Mar 28;278(13):11471-9. doi: 10.1074/jbc.M209723200. Epub 2003 
      Jan 7.