Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription

Sunita K. Agarwal; Siradanahalli C. Guru; Christina Heppner; Michael R. Erdos; Regina M. Collins; Sylvia Y. Park; Suraj Saggar; Settara C. Chandrasekharappa; Francis S. Collins; Allen M. Spiegel; Stephen J. Marx; A. Lee Burns

doi:10.1016/S0092-8674(00)80967-8

Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription

Sunita K. Agarwal, Siradanahalli C. Guru, Christina Heppner, Michael R. Erdos, Regina M. Collins, Sylvia Y. Park, Suraj Saggar, Settara C. Chandrasekharappa, Francis S. Collins, Allen M. Spiegel, Stephen J. Marx, A. Lee Burns

Research output: Contribution to journal › Article › peer-review

545 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	143-152
Number of pages	10
Journal	Cell
Volume	96
Issue number	1
DOIs	https://doi.org/10.1016/S0092-8674(00)80967-8
State	Published - Jan 8 1999
Externally published	Yes

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/S0092-8674(00)80967-8

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@article{eca671d248d64747a2d337b1e9233eba,

title = "Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription",

abstract = "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.",

author = "Agarwal, {Sunita K.} and Guru, {Siradanahalli C.} and Christina Heppner and Erdos, {Michael R.} and Collins, {Regina M.} and Park, {Sylvia Y.} and Suraj Saggar and Chandrasekharappa, {Settara C.} and Collins, {Francis S.} and Spiegel, {Allen M.} and Marx, {Stephen J.} and {Lee Burns}, A.",

note = "Funding Information: We thank Dr. George Poy for DNA sequencing and Mary Beth Kester for technical assistance. We also thank Dr. Rodrigo Bravo for permission to use the mouse JunD plasmid, and Dr. Kevin Gardner for sharing reagents. C. H. was supported by a grant from The Fritz Thyssen Stiftung (Germany).",

year = "1999",

month = jan,

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doi = "10.1016/S0092-8674(00)80967-8",

language = "English (US)",

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pages = "143--152",

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TY - JOUR

T1 - Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription

AU - Agarwal, Sunita K.

AU - Guru, Siradanahalli C.

AU - Heppner, Christina

AU - Erdos, Michael R.

AU - Collins, Regina M.

AU - Park, Sylvia Y.

AU - Saggar, Suraj

AU - Chandrasekharappa, Settara C.

AU - Collins, Francis S.

AU - Spiegel, Allen M.

AU - Marx, Stephen J.

AU - Lee Burns, A.

N1 - Funding Information: We thank Dr. George Poy for DNA sequencing and Mary Beth Kester for technical assistance. We also thank Dr. Rodrigo Bravo for permission to use the mouse JunD plasmid, and Dr. Kevin Gardner for sharing reagents. C. H. was supported by a grant from The Fritz Thyssen Stiftung (Germany).

PY - 1999/1/8

Y1 - 1999/1/8

N2 - 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.

AB - 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.

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DO - 10.1016/S0092-8674(00)80967-8

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AN - SCOPUS:0033534510

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JO - Cell

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Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription

Abstract

ASJC Scopus subject areas

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