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

Yu Chiau Shyu, Tung Liang Lee, Xin Chen, Pang Hung Hsu, Shau Ching Wen, Yi Wei Liaw, Chi Huan Lu, Po Yen Hsu, Mu Jie Lu, JauLang Hwang, Ming Daw Tsai, Ming Jing Hwang, Jim Ray Chen, Che Kun James Shen

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7 Citations (Scopus)

Abstract

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 PKCθ, phosphorylation of EKLF at S68 by P-PKCθ(S676), and sumoylation of EKLF at K74. The latter EKLF modifications modulate its interactions with a cytoplasmic ankyrin-repeat-protein FOE and importinβ1, 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.

Original languageEnglish
Pages (from-to)409-422
Number of pages14
JournalDevelopmental Cell
Volume28
Issue number4
DOIs
Publication statusPublished - Feb 24 2014
Externally publishedYes

ASJC Scopus subject areas

  • Developmental Biology

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  • Cite this

    Shyu, Y. C., Lee, T. L., Chen, X., Hsu, P. H., Wen, S. C., Liaw, Y. W., Lu, C. H., Hsu, P. Y., Lu, M. J., Hwang, J., Tsai, M. D., Hwang, M. J., Chen, J. R., & James Shen, C. K. (2014). Tight regulation of a timed nuclear import wave of EKLF by PKCθ and FOE during Pro-E to Baso-E transition. Developmental Cell, 28(4), 409-422. https://doi.org/10.1016/j.devcel.2014.01.007