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

Tina L Tootle; Philina S Lee; Ilaria Rebay

doi:10.1242/dev.00312

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

Journal article

Open access

Peer reviewed

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

Tina L Tootle, Philina S Lee and Ilaria Rebay

Development (Cambridge), Vol.130(5), pp.845-857

03/2003

DOI: 10.1242/dev.00312

PMID: 12538513

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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.

Drosophila melanogaster - physiology

Embryo, Nonmammalian - anatomy & histology

Active Transport, Cell Nucleus - physiology

ras Proteins - metabolism

Drosophila Proteins - metabolism

Drosophila melanogaster - genetics

Receptors, Cytoplasmic and Nuclear

Transcription, Genetic

Eye Proteins - genetics

Organisms, Genetically Modified

Embryo, Nonmammalian - physiology

Nuclear Proteins - genetics

Insect Proteins - metabolism

Genes, Reporter

Repressor Proteins - metabolism

DNA-Binding Proteins

Proto-Oncogene Proteins - metabolism

Cells, Cultured

Gene Expression Regulation

Insect Proteins - genetics

Intracellular Signaling Peptides and Proteins

Repressor Proteins - genetics

Nuclear Proteins - metabolism

Proto-Oncogene Proteins - genetics

Nerve Tissue Proteins

Drosophila melanogaster - ultrastructure

Nuclear Localization Signals

Down-Regulation - physiology

Carrier Proteins - genetics

Animals

Carrier Proteins - metabolism

Karyopherins - metabolism

Eye Proteins - metabolism

Models, Biological

Karyopherins - genetics

Protein Binding

Signal Transduction - physiology

Transcription Factors

Drosophila Proteins - genetics

Mitogen-Activated Protein Kinases - metabolism

Details

Title: Subtitle: CRM1-mediated nuclear export and regulated activity of the Receptor Tyrosine Kinase antagonist YAN require specific interactions with MAE
Creators: Tina L Tootle - Whitehead Institute, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
Philina S Lee
Ilaria Rebay
Resource Type: Journal article
Publication Details: Development (Cambridge), Vol.130(5), pp.845-857
Publisher: England
DOI: 10.1242/dev.00312
PMID: 12538513
ISSN: 0950-1991
eISSN: 1477-9129
Language: English
Date published: 03/2003
Academic Unit: Anatomy and Cell Biology
Record Identifier: 9984025688602771

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