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Publication : Tight regulation of a timed nuclear import wave of EKLF by PKCθ and FOE during Pro-E to Baso-E transition.

First Author  Shyu YC Year  2014
Journal  Dev Cell Volume  28
Issue  4 Pages  409-22
PubMed ID  24576425 Mgi Jnum  J:316274
Mgi Id  MGI:6835022 Doi  10.1016/j.devcel.2014.01.007
Citation  Shyu YC, et al. (2014) Tight regulation of a timed nuclear import wave of EKLF by PKCtheta and FOE during Pro-E to Baso-E transition. Dev Cell 28(4):409-22
abstractText  Erythropoiesis is a highly regulated process during which BFU-E are differentiated into RBCs through CFU-E, Pro-E, PolyCh-E, OrthoCh-E, and reticulocyte stages. Uniquely, most erythroid-specific genes are activated during the Pro-E to Baso-E transition. We show that a wave of nuclear import of the erythroid-specific transcription factor EKLF occurs during the Pro-E to Baso-E transition. We further demonstrate that this wave results from a series of finely tuned events, including timed activation of PKCtheta, phosphorylation of EKLF at S68 by P-PKCtheta(S676), and sumoylation of EKLF at K74. The latter EKLF modifications modulate its interactions with a cytoplasmic ankyrin-repeat-protein FOE and importinbeta1, respectively. The role of FOE in the control of EKLF nuclear import is further supported by analysis of the subcellular distribution patterns of EKLF in FOE-knockout mice. This study reveals the regulatory mechanisms of the nuclear import of EKLF, which may also be utilized in the nuclear import of other factors.
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