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; Jau Lang Hwang; Ming Daw Tsai; Ming Jing Hwang; Jim Ray Chen; Che Kun James Shen

doi:10.1016/j.devcel.2014.01.007

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, Jau Lang Hwang, Ming Daw Tsai, Ming Jing Hwang, Jim Ray Chen, Che Kun James Shen

Experimental Radiation Oncology

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

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 language	English (US)
Pages (from-to)	409-422
Number of pages	14
Journal	Developmental cell
Volume	28
Issue number	4
DOIs	https://doi.org/10.1016/j.devcel.2014.01.007
State	Published - Feb 24 2014

ASJC Scopus subject areas

Molecular Biology
General Biochemistry, Genetics and Molecular Biology
Developmental Biology
Cell Biology

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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. L., 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

@article{a9a8b358ec654b67956fe9751c216a4d,

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

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.",

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

note = "Funding Information: We thank Si-Tse Jiang, Chun-Yuan Ting, Nan-Shih Liao, Jan-Mou Lee, Yii-Jenq Lan, Hsiu-Ming Shih, Hsiu-Ling Chang, and Ting-Shuo Huang for generously sharing reagents and providing assistance, and our lab colleagues Yu-Szu Huang, Wei-Chang Lee, Yuh-Jay Huang, Hsin Chen, Wei-Yuan Hsiao, and Shin-Chen Hou for their help and discussions. We thank Doug Higgs, Doug Engel, and Nick Proudfoot for their encouragement and helpful suggestions. This research was supported by the National Health Research Institute (NHRI-EX103-10011SI), the National Science Council, and Academia Sinica. ",

year = "2014",

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doi = "10.1016/j.devcel.2014.01.007",

language = "English (US)",

volume = "28",

pages = "409--422",

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T1 - Tight regulation of a timed nuclear import wave of EKLF by PKCθ and FOE during Pro-E to Baso-E transition

AU - Shyu, Yu Chiau

AU - Lee, Tung Liang

AU - Chen, Xin

AU - Hsu, Pang Hung

AU - Wen, Shau Ching

AU - Liaw, Yi Wei

AU - Lu, Chi Huan

AU - Hsu, Po Yen

AU - Lu, Mu Jie

AU - Hwang, Jau Lang

AU - Tsai, Ming Daw

AU - Hwang, Ming Jing

AU - Chen, Jim Ray

AU - James Shen, Che Kun

N1 - Funding Information: We thank Si-Tse Jiang, Chun-Yuan Ting, Nan-Shih Liao, Jan-Mou Lee, Yii-Jenq Lan, Hsiu-Ming Shih, Hsiu-Ling Chang, and Ting-Shuo Huang for generously sharing reagents and providing assistance, and our lab colleagues Yu-Szu Huang, Wei-Chang Lee, Yuh-Jay Huang, Hsin Chen, Wei-Yuan Hsiao, and Shin-Chen Hou for their help and discussions. We thank Doug Higgs, Doug Engel, and Nick Proudfoot for their encouragement and helpful suggestions. This research was supported by the National Health Research Institute (NHRI-EX103-10011SI), the National Science Council, and Academia Sinica.

PY - 2014/2/24

Y1 - 2014/2/24

N2 - 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.

AB - 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.

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DO - 10.1016/j.devcel.2014.01.007

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AN - SCOPUS:84894304557

SN - 1534-5807

VL - 28

SP - 409

EP - 422

JO - Developmental cell

JF - Developmental cell

IS - 4

ER -

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

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