Antagonistic regulation of Yan nuclear export by Mae and Crm1 may increase the stringency of the Ras response.
Phosphorylation of Yan, a major target of Ras signaling, leads to Crm1-dependent Yan nuclear export, a response that is regulated by Yan polymerization. Yan SAM (sterile alpha motif) domain mutations preventing polymerization result in Ras-independent, but Crm1-dependent Yan nuclear export, suggesting that polymerization prevents Yan export. Mae, which depolymerizes Yan, competes with Crm1 for binding to Yan. Phosphorylation of Yan favors Crm1 in this competition and counteracts inhibition of nuclear export by Mae. These findings suggest that, prior to Ras activation, the Mae/Yan interaction blocks premature nuclear export of Yan monomers. After activation, transcriptional up-regulation of Mae apparently leads to complete depolymerization and export of Yan.
Song
Haiyun
H
Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095, USA.
Nie
Minghua
M
Qiao
Feng
F
Bowie
James U
JU
Courey
Albert J
AJ
D000818:Animals; D001667:Binding, Competitive; D002467:Cell Nucleus / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism* / Q000502:physiology*; D005136:Eye Proteins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D028884:Karyopherins / Q000502:physiology*; D009154:Mutation; D010766:Phosphorylation; D021381:Protein Transport; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction; D018631:ras Proteins / Q000378:metabolism*; D000097606:Exportin 1 Protein
D029721:Drosophila Proteins; D005136:Eye Proteins; D047908:Intracellular Signaling Peptides and Proteins; D028884:Karyopherins; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; D018631:ras Proteins; D000097606:Exportin 1 Protein; C076188:AOP protein, Drosophila; C428945:edl protein, Drosophila