caa a22 4500 475845862 CHVBK 20180406123914.0 cr unu---uuuuu 170329e20000301xx s 000 0 eng 10.1007/PL00000703 doi (NATIONALLICENCE)springer-10.1007/PL00000703 Nucleocytoplasmic shuttling and the control of NF-AT signaling [Elektronische Daten] [J. Zhu, F. McKeon*] Abstract.: The nuclear factors of activated T cells (NF-ATs) constitute a family of transcription factors that transduce calcium signals in the immune, cardiac, muscular and nervous systems. Like their distant relatives of the Rel family, including NF-κB, NF-ATs are cytoplasmic in resting cells and activated by means of induced nuclear import. Unlike NF-κB, however, NF-ATs show highly dynamic nuclear shuttling properties that have important implications for graded signaling by these molecules. This review focuses on recent advances in deciphering mechanisms by which calcium signaling regulates the nucleo-cytoplasmic shuttling and therefore transactivation functions of the NF-ATs. These discoveries highlight the interplay between nuclear import and export signals on NF-ATs, and the roles of the calcium-activated phosphatase calcineurin and NF-AT kinases in controlling the activity of these signals. They also reveal that NF-ATs, as well as other transcription factors controlled at the level of nuclear import, face the very real prospect of futile cycling across the nuclear envelope as a consequence of conflicting nuclear import and export signals. We discuss the molecular mechanisms by which calcineurin suppresses futile cycling, as well as the major challenges to our understanding of NF-AT signaling in diverse biological systems. Birkhäuser Verlag Basel,, 2000 Key words. NF-AT nationallicence nuclear factor of activated T cells nationallicence transcription factor nationallicence calcium nationallicence calcineurin nationallicence CRM1 nationallicence casein kinase I nationallicence NLS nationallicence nuclear localization signal nationallicence NES nationallicence nuclear export signal nationallicence Zhu J. Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston (Massachusetts 02115, USA), Fax +1 617 432 6655, e-mail: frank_mckeon@hms.harvard.edu, US aut McKeon* F. Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston (Massachusetts 02115, USA), Fax +1 617 432 6655, e-mail: frank_mckeon@hms.harvard.edu, US aut https://doi.org/10.1007/PL00000703 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/PL00000703 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zhu J. Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston (Massachusetts 02115, USA), Fax +1 617 432 6655, e-mail: frank_mckeon@hms.harvard.edu, US aut NATIONALLICENCE 700 1- McKeon* F. Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston (Massachusetts 02115, USA), Fax +1 617 432 6655, e-mail: frank_mckeon@hms.harvard.edu, US aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer