EIF3 p170, a mediator of mimosine effect on protein synthesis and cell cycle progression.
l-Mimosine, a plant amino acid, can reversibly block mammalian cells at late G1 phase and has been suggested to affect translation of mRNAs such as p27, the CDK inhibitor. However, the mechanism of this effect is not known. Regulation of translation generally occurs at the initiation step that, in mammalian cells, is a complex process that requires multiple eukaryotic initiation factors (eIFs) and ribosome. The effects of mimosine on initiation factors or regulators consequently will influence translation initiation. P170, a putative subunit of eIF3, has been suggested to be nonessential for eIF3 function to form preinitiation complexes and it may function as a regulator for translation of a subset of mRNAs. In this article, we tested this hypothesis and investigated whether eIF3 p170 mediates mimosine effect on mRNA translation. We found that p170 translation was dramatically reduced by mimosine due to its iron-chelating function. The decreased expression of p170 by mimosine caused diminished de novo synthesis of tyrosinated alpha-tubulin and elevated translation of p27 before cell cycle arrest. These observations suggest that p170 is likely an early response gene to mimosine treatment and a mediator for mimosine effect on mRNA translation. The effect of p170 on the synthesis of tyrosinated alpha-tubulin and p27 in a reciprocal manner also suggests that p170 functions as a regulator for mRNA translation.
Dong
Zizheng
Z
Department of Pharmacology and Toxicology, Indiana University Cancer Center and Walther Oncology Center/Walther Cancer Institute, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Zhang
Jian-Ting
JT
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D039621:Eukaryotic Initiation Factor-3 / Q000378:metabolism*; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008898:Mimosine / Q000494:pharmacology; D041681:NIH 3T3 Cells; D014176:Protein Biosynthesis / Q000502:physiology*; D021122:Protein Subunits / Q000378:metabolism*; D015398:Signal Transduction; D014404:Tubulin / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D039621:Eukaryotic Initiation Factor-3; D021122:Protein Subunits; D014404:Tubulin; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D008898:Mimosine