CRM1-mediated nuclear export and regulated activity of the Receptor Tyrosine Kinase antagonist YAN require specific interactions with MAE.
ETS family transcription factors serve as downstream effectors of signal transduction pathways, mediating cellular proliferation, differentiation and, when misregulated, tumorigenesis. The transcriptional repressor YAN prevents inappropriate responses to Receptor Tyrosine Kinase signaling by outcompeting POINTED for access to target gene promoters. We demonstrate that the molecular mechanism underlying downregulation of YAN involves CRM1-mediated nuclear export and define a novel role in this context for MAE, a co-factor previously implicated in facilitating MAPK phosphorylation of YAN. In addition to promoting YAN downregulation, MAE also participates in an inhibitory feedback loop that attenuates POINTED-P2 activation. Thus, we propose that MAE plays multiple independent roles in fine-tuning the levels of POINTED and YAN activity in accordance with changing RTK signaling conditions.
Tootle
Tina L
TL
Whitehead Institute, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Lee
Philina S
PS
Rebay
Ilaria
I
D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D015536:Down-Regulation / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology / Q000648:ultrastructure; D004625:Embryo, Nonmammalian / Q000033:anatomy & histology / Q000502:physiology; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D009419:Nerve Tissue Proteins; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D030781:Organisms, Genetically Modified; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors; D014158:Transcription, Genetic; D018631:ras Proteins / Q000378:metabolism; D000097606:Exportin 1 Protein
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D005136:Eye Proteins; D019476:Insect Proteins; D047908:Intracellular Signaling Peptides and Proteins; D028884:Karyopherins; D020928:Mitogen-Activated Protein Kinases; D009419:Nerve Tissue Proteins; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; D014157:Transcription Factors; D018631:ras Proteins; D000097606:Exportin 1 Protein; C076188:AOP protein, Drosophila; C428945:edl protein, Drosophila; C083884:pnt protein, Drosophila