Direct association of tristetraprolin with the nucleoporin CAN/Nup214.
Tristetraprolin (TTP) is a widely expressed, zinc finger-containing protein that has been implicated in the regulation of TNFalpha production in mice. Stimulus-dependent cytoplasmic translocation of TTP has been demonstrated in several cells. In this report we used the yeast two-hybrid screen to identify proteins able to interact with full length, human TTP. One of the isolated TTP-interacting clones encoded the FG repeat region of the nuclear pore protein Nup214. Full length Nup214 co-precipitated with TTP from resting and LPS-stimulated THP-1 cells, indicating that this interaction occurred in intact cells. The ability of TTP to associate with Nup214 was dependent on two intact zinc fingers within TTP. In contrast to wild type TTP that localized primarily in the cytosol, a mutant unable to associate with Nup214 localized throughout the cell, suggesting that the interaction with Nup214 regulates TTP localization.
Carman
Julie A
JA
Lawrenceville Discovery Biology, Bristol-Myers Squibb, Princeton, NJ 08543, USA. julie.carman@bms.com
Nadler
Steven G
SG
D021581:Active Transport, Cell Nucleus; D000818:Animals; D019556:COS Cells; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006801:Humans; D017874:Immediate-Early Proteins / Q000737:chemistry* / Q000378:metabolism; D018613:Microscopy, Confocal; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry* / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D013997:Time Factors; D051816:Tristetraprolin; D020798:Two-Hybrid System Techniques; D016335:Zinc Fingers
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D017874:Immediate-Early Proteins; C085914:NUP214 protein, human; D028861:Nuclear Pore Complex Proteins; D051816:Tristetraprolin; C497552:ZFP36 protein, human