PMID- 20544796
OWN - NLM
STAT- MEDLINE
DCOM- 20101115
LR  - 20201209
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 110
IP  - 5
DP  - 2010 Aug 1
TI  - alpha4 phosphoprotein interacts with EDD E3 ubiquitin ligase and poly(A)-binding 
      protein.
PG  - 1123-9
LID - 10.1002/jcb.22624 [doi]
AB  - Mammalian alpha4 phosphoprotein, the homolog of yeast Tap42, is a component of 
      the mammalian target-of-rapamycin (mTOR) pathway that regulates ribogenesis, the 
      initiation of translation, and cell-cycle progression. alpha4 is known to 
      interact with the catalytic subunit of protein phosphatase 2A (PP2Ac) and to 
      regulate PP2A activity. Using alpha4 as bait in yeast two-hybrid screening of a 
      human K562 erythroleukemia cDNA library, EDD (E3 isolated by differential 
      display) E3 ubiquitin ligase was identified as a new protein partner of alpha4. 
      EDD is the mammalian ortholog of Drosophila hyperplastic discs gene (hyd) that 
      controls cell proliferation during development. The EDD protein contains a PABC 
      domain that is present in poly(A)-binding protein (PABP), suggesting that PABP 
      may also interact with alpha4. PABP recruits translation factors to the 
      poly(A)-tails of mRNAs. In the present study, immunoprecipitation/immunoblotting 
      (IP/IB) analyses showed a physical interaction between alpha4 and EDD in rat Nb2 
      T-lymphoma and human MCF-7 breast cancer cell lines. alpha4 also interacted with 
      PABP in Nb2, MCF-7 and the human Jurkat T-leukemic and K562 myeloma cell lines. 
      COS-1 cells, transfected with Flag-tagged-pSG5-EDD, gave a (Flag)-EDD-alpha4 
      immunocomplex. Furthermore, deletion mutants of alpha4 were constructed to 
      determine the binding site for EDD. IP/IB analysis showed that EDD bound to the 
      C-terminal region of alpha4, independent of the alpha4-PP2Ac binding site. 
      Therefore, in addition to PP2Ac, alpha4 interacts with EDD and PABP, suggesting 
      its involvement in multiple steps in the mTOR pathway that leads to translation 
      initiation and cell-cycle progression.
CI  - Published 2010 Wiley-Liss, Inc.
FAU - McDonald, William J
AU  - McDonald WJ
AD  - Faculty of Medicine, Department of Biochemistry & Molecular Biology, Dalhousie 
      University, Halifax, Nova Scotia, Canada.
FAU - Sangster, Shirley M
AU  - Sangster SM
FAU - Moffat, Lori D
AU  - Moffat LD
FAU - Henderson, Michelle J
AU  - Henderson MJ
FAU - Too, Catherine K L
AU  - Too CK
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (IGBP1 protein, human)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Molecular Chaperones)
RN  - 0 (Phosphoproteins)
RN  - 0 (Poly(A)-Binding Proteins)
RN  - EC 2.3.2.26 (UBR5 protein, human)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 3.1.3.16 (Protein Phosphatase 2)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - COS Cells
MH  - Cell Line, Tumor
MH  - Chlorocebus aethiops
MH  - Humans
MH  - Immunoblotting
MH  - Immunoprecipitation
MH  - Intracellular Signaling Peptides and Proteins/genetics/*metabolism
MH  - Jurkat Cells
MH  - K562 Cells
MH  - Molecular Chaperones
MH  - Phosphoproteins/genetics/*metabolism
MH  - Poly(A)-Binding Proteins/genetics/*metabolism
MH  - Protein Binding
MH  - Protein Phosphatase 2/genetics/metabolism
MH  - Two-Hybrid System Techniques
MH  - Ubiquitin-Protein Ligases/genetics/*metabolism
EDAT- 2010/06/15 06:00
MHDA- 2010/11/16 06:00
CRDT- 2010/06/15 06:00
PHST- 2010/06/15 06:00 [entrez]
PHST- 2010/06/15 06:00 [pubmed]
PHST- 2010/11/16 06:00 [medline]
AID - 10.1002/jcb.22624 [doi]
PST - ppublish
SO  - J Cell Biochem. 2010 Aug 1;110(5):1123-9. doi: 10.1002/jcb.22624.