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.
authors.affiliation: Institute of Biopharmaceutical Sciences, National Yang-Ming University, Beitou, Taipei 112, Taiwan, ROC; Department of Education and Research, Taipei City Hospital, Da'an, Taipei 103, Taiwan, ROC; Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, Taiwan 115, ROC. Electronic address: ycshyu@ym.edu.tw.
authors.forename: Yu-Chiau
authors.initials: YC
authors.lastname: Shyu
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, Taiwan 115, ROC.
authors.forename: Tung-Liang
authors.initials: TL
authors.lastname: Lee
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, Taiwan 115, ROC.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: The Genomics Research Center, Academia Sinica, Nankang, Taipei 115, Taiwan, ROC.
authors.forename: Pang-Hung
authors.initials: PH
authors.lastname: Hsu
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, Taiwan 115, ROC.
authors.forename: Shau-Ching
authors.initials: SC
authors.lastname: Wen
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, Taiwan 115, ROC.
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Liaw
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, Taiwan 115, ROC.
authors.forename: Chi-Huan
authors.initials: CH
authors.lastname: Lu
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, Taiwan 115, ROC.
authors.forename: Po-Yen
authors.initials: PY
authors.lastname: Hsu
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, Taiwan 115, ROC.
authors.forename: Mu-Jie
authors.initials: MJ
authors.lastname: Lu
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, Taiwan 115, ROC.
authors.forename: JauLang
authors.initials: J
authors.lastname: Hwang
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Nankang, Taipei 115, Taiwan, ROC.
authors.forename: Ming-Daw
authors.initials: MD
authors.lastname: Tsai
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Nankang, Taipei 115, Taiwan, ROC.
authors.forename: Ming-Jing
authors.initials: MJ
authors.lastname: Hwang
authors.affiliation: Department of Pathology, Keelung Chang Gung Memorial Hospital, Anle, Keelung 204, Taiwan, ROC; College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan 259, Taiwan, ROC.
authors.forename: Jim-Ray
authors.initials: JR
authors.lastname: Chen
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, Taiwan 115, ROC. Electronic address: ckshen@imb.sinica.edu.tw.
authors.forename: Che-Kun James
authors.initials: CK
authors.lastname: Shen
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004920:Erythropoiesis / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D011493:Protein Kinase C / Q000378:metabolism*; D013997:Time Factors
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C587997:FOE protein, mouse; D051741:Kruppel-Like Transcription Factors; C080774:erythroid Kruppel-like factor; D011493:Protein Kinase C