JunD-menin interaction regulates c-Jun-mediated AP-1 transactivation

Area of Science:

• Molecular Biology
• Cell Biology
• Genetics

Background:

• The gene for multiple endocrine neoplasia type 1 (MEN1) encodes the menin protein.
• Menin's role in tumorigenesis and its interaction with transcription factors like AP-1 (including JunD and c-Jun) requires further elucidation.
• Understanding menin's molecular mechanisms is crucial for comprehending its physiological functions.

Purpose of the Study:

• To investigate the effects of wild-type and mutant menin proteins on AP-1 transactivation.
• To elucidate the molecular mechanisms underlying menin's interaction with AP-1 transcription factors.
• To explore the physiological significance of menin in regulating gene transcription.

Main Methods:

• Utilized COS cells for studying protein-protein interactions and transactivation assays.
• Employed electrophoretic mobility shift assays (EMSA) to assess DNA-binding activity.
• Investigated dose-dependent effects of wild-type and mutant menin on JunD- and c-Jun-mediated transactivation.

Main Results:

• Wild-type menin suppressed JunD-mediated transactivation and enhanced c-Jun-mediated transactivation in a dose-dependent manner.
• These regulatory effects were diminished or abolished in all examined menin mutants.
• Menin did not alter the DNA-binding affinity of c-Jun, and the JunD amino-terminal fragment interfered with menin's enhancement of c-Jun activity.

Conclusions:

• Menin exhibits differential regulation of AP-1 transcription factors, suppressing JunD while enhancing c-Jun activity.
• Menin's interaction with JunD may negatively modulate its enhancing effect on c-Jun transactivation.
• Mutations in menin likely impair its ability to regulate AP-1 activity, potentially contributing to tumorigenesis in MEN1.