alpha 4 Phosphoprotein Interacts With EDD E3 Ubiquitin Ligase and Poly(A)-Binding Protein

作者：McDonald William J; Sangster Shirley M; Moffat Lori D; Henderson Michelle J; Too Catherine K L^*

来源：Journal of Cellular Biochemistry, 2010, 110(5): 1123-1129.

DOI：10.1002/jcb.22624

• alpha 4 PHOSPHOPROTEIN
• EDD E3 UBIQUITIN LIGASE
• POLY(A)-BINDING PROTEIN

Mammalian alpha 4 phosphoprotein, the homolog of yeast Tap42. is a component or the mammalian target-of-rapamycin (mTOR) pathway that regulates ribogenesis, the initiation of translation, and cell-cycle progression alpha 4 is known to interact with the catalytic subunit of protein phosphatase 2A (PP2Ac) and to regulate PP2A activity. Using alpha 4 as ban 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 alpha 4 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 alpha 4. 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 alpha 4 and EDD in rat Nb2 T-lymphoma and human MCF-7 breast cancer cell lines alpha 4 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-alpha 4 immunocomplex Furthermore. deletion mutants of alpha 4 were constructed to determine the binding sue for EDD IP/IB analysis showed that EDD bound to the C-terminal region of alpha 4, independent of the alpha 4-PP2Ac binding site Therefore, in addition to PP2Ac, alpha 4 interacts with EDD and PABP. suggesting its involvement in multiple steps in the mTOR pathway that leads to translation Initiation and cell-cycle progression J. Cell. Biochem 110 1123-1129, 2010.

• 出版日期2010-8-1