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Development 130 (5): 845-857

CRM1-mediated nuclear export and regulated activity of the Receptor Tyrosine Kinase antagonist YAN require specific interactions with MAE

Tina L. Tootle1,2, Philina S. Lee2, and Ilaria Rebay1,2,*

1 Whitehead Institute, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
2 Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA

* Author for correspondence (e-mail: rebay{at}wi.mit.edu)

Accepted for publication 27 November 2002.

Abstract: 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.

Key Words: Receptor tyrosine kinase • Nuclear export • ETS transcription factor • Drosophila

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