Itch regulates p45/NF-E2 in vivo by Lys63-linked ubiquitination.

The hematopoietic-specific transcription factor p45/NF-E2 is an important transcriptional activator in the erythroid and megakaryocytic lineages. We describe the first in vivo evidence for the interaction between p45/NF-E2 and the E3 ubiquitin ligase Itch, and the subsequent ubiquitination of p45/NF-E2 by Itch. Interestingly, Itch suppressed the transactivation activity of p45/NF-E2 ...
by adding a Lys63-linked polyubiquitin chain. Confocal microscopy revealed that ubiquitinated p45/NF-E2 became localized in the cytoplasm when Itch was over-expressed. Thus, Itch-mediated ubiquitination of p45/NF-E2 does not target the protein for proteasomal degradation, but instead retains p45/NF-E2 in the cytoplasm, where it cannot function as a transactivator. Finally, we suggest that this Itch-dependent p45/NF-E2 ubiquitination mechanism may regulate NF-E2 function during the development of hematopoietic cell lineages.
Mesh Terms:
Cell Line, Cytoplasm, Humans, Lysine, NF-E2 Transcription Factor, p45 Subunit, Polyubiquitin, Repressor Proteins, Transcriptional Activation, Ubiquitin-Protein Ligases, Ubiquitination
Biochem. Biophys. Res. Commun.
Date: Oct. 24, 2008
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