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Updated: Sep 27, 2026

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
Published on: November 15, 2013
CRM1-mediated nuclear export and regulated activity of the Receptor Tyrosine Kinase antagonist YAN require specific
Tina L Tootle1, Philina S Lee, Ilaria Rebay
1Whitehead Institute, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
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.
Insights
The study reveals how MAE protein regulates YAN and POINTED activity, crucial for controlling cell growth and preventing cancer by fine-tuning Receptor Tyrosine Kinase (RTK) signaling.
Area of Science:
- Molecular Biology
- Cell Signaling
- Cancer Research
Background:
- ETS transcription factors regulate cell processes and are implicated in tumorigenesis when misregulated.
- YAN acts as a transcriptional repressor, balancing Receptor Tyrosine Kinase (RTK) signaling.
- Understanding YAN regulation is key to controlling cell proliferation and differentiation.
Purpose of the Study:
- To elucidate the molecular mechanism of YAN downregulation.
- To define the role of MAE, a co-factor, in YAN regulation and RTK signaling.
- To investigate MAE's function in feedback loops controlling ETS factor activity.
Main Methods:
- Investigated CRM1-mediated nuclear export of YAN.
- Assessed the role of MAE in YAN phosphorylation and downregulation.
- Analyzed MAE's impact on POINTED-P2 activation.
Main Results:
- Demonstrated CRM1-mediated nuclear export as a key mechanism for YAN downregulation.
- Identified MAE as a crucial co-factor promoting YAN downregulation.
- Discovered MAE's dual role in YAN regulation and an inhibitory feedback loop on POINTED-P2.
Conclusions:
- MAE plays multiple, independent roles in modulating YAN and POINTED activity.
- MAE fine-tunes ETS factor levels in response to RTK signaling.
- This regulation is critical for preventing inappropriate cellular responses and potential tumorigenesis.
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