Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription.
MEN1 is a tumor suppressor gene that encodes a 610 amino acid nuclear protein (menin) of previously unknown function. Using a yeast two-hybrid screen with menin as the bait, we have identified the transcription factor JunD as a direct menin-interacting partner. Menin did not interact directly with other Jun and Fos family members. The menin-JunD interaction was confirmed in vitro and in vivo. Menin repressed transcriptional activation mediated by JunD fused to the Gal4 DNA-binding domain from a Gal4 responsive reporter, or by JunD from an AP1-responsive reporter. Several naturally occurring and clustered MEN1 missense mutations disrupted menin interaction with JunD. These observations suggest that menin's tumor suppressor function involves direct binding to JunD and inhibition of JunD activated transcription.
Agarwal
S K
SK
Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. sunitaa@amb.niddk.nih.gov
Guru
S C
SC
Heppner
C
C
Erdos
M R
MR
Collins
R M
RM
Park
S Y
SY
Saggar
S
S
Chandrasekharappa
S C
SC
Collins
F S
FS
Spiegel
A M
AM
Marx
S J
SJ
Burns
A L
AL
D000818:Animals; D001665:Binding Sites; D006367:HeLa Cells; D006801:Humans; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D011233:Precipitin Tests; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015533:Transcriptional Activation; D015003:Yeasts