Transforming acidic coiled-coil protein 3 (TACC3) controls friend of GATA-1 (FOG-1) subcellular localization and regulates the association between GATA-1 and FOG-1 during hematopoiesis.
Physical association between the transcription factor GATA-1 and the cofactor, Friend of GATA-1 (FOG-1), is essential for the differentiation of two blood cell types, erythroid cells and megakaryocytes. However, little is known regarding the mechanisms that modulate their interaction within cells. In the present study, we have identified TACC3 as a FOG-1-interacting protein. Transforming acidic coiled-coil protein 3 (TACC3), a protein that is highly expressed in hematopoietic cells, has been reported to have a critical role in the expansion of immature hematopoietic progenitors. We show that TACC3 affects FOG-1 nuclear localization, altering the interaction between GATA-1 and FOG-1. However, GATA-1 competes with TACC3 in the interaction with FOG-1. We observe that high levels of TACC3 inhibit the function of FOG-1 as a transcriptional cofactor of GATA-1. Furthermore, forced expression of TACC3 to levels similar to those found in progenitor cells delays terminal maturation of MEL and G1ER cells, two cell models of erythroid cell development. We suggest a role for TACC3 in regulating the cellular distribution of FOG-1 and thus the direct interaction of GATA-1 and FOG-1 as a mechanism to control the transition between expansion of multipotential progenitor cell populations and final stages of erythroid maturation.
Garriga-Canut
Mireia
M
Division of Hematology/Oncology, Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School and Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA.
Orkin
Stuart H
SH
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050981:Erythroid-Specific DNA-Binding Factors; D005326:Fetal Proteins / Q000378:metabolism*; D050982:GATA1 Transcription Factor; D006410:Hematopoiesis / Q000502:physiology*; D051379:Mice; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport / Q000502:physiology; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D005326:Fetal Proteins; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; C418485:TACC3 protein, mouse; D014157:Transcription Factors; C107310:Zfpm1 protein, mouse