Transcription factor JunD, deprived of menin, switches from growth suppressor to growth promoter

Sunita K. Agarwal, Elizabeth A. Novotny, Judy S. Crabtree, Jonathan B. Weitzman, Moshe Yaniv, A. Lee Burns, Settara C. Chandrasekharappa, Francis S. Collins, Allen M. Spiegel, Stephen J. Marx

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

Different components of the AP1 transcription factor complex appear to have distinct effects on cell proliferation and transformation. In contrast to other AP1 components, JunD has been shown to inhibit cell proliferation. Also, in prior studies, JunD alone bound menin, product of the MEN1 tumor suppressor gene, and JunD's transcriptional activity was inhibited by menin, suggesting that JunD might achieve all or most of its unique properties through binding to menin. Analyses of JunD and menin effects on proliferation, morphology, and cyclin D1 in stable cell lines unmasked an unexpected growth promoting activity of JunD. Whereas stable overexpression of wild-type (wt) mouse JunD in JunD -/- immortalized fibroblasts inhibited their proliferation and reverted their transformed-like phenotype, overexpression of a missense mouse JunD mutant (mJunDG42E) with disabled binding to menin showed opposite or growth promoting effects. Similarly, stable overexpression of wt mouse JunD in wt immortalized fibroblasts inhibited growth. In contrast, its overexpression in Men1-/- immortalized fibroblasts enhanced their already transformed-like characteristics. To conclude, JunD changed from growth suppressor to growth promoter when its binding to menin was prevented by a JunD mutant unable to bind menin or by Men1-null genetic background.

Original languageEnglish (US)
Pages (from-to)10770-10775
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number19
DOIs
StatePublished - Sep 16 2003
Externally publishedYes

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Transcription Factors
Fibroblasts
Growth
Cell Proliferation
Multiple Endocrine Neoplasia Type 1
Cyclin D1
Tumor Suppressor Genes
Phenotype
Cell Line

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Transcription factor JunD, deprived of menin, switches from growth suppressor to growth promoter. / Agarwal, Sunita K.; Novotny, Elizabeth A.; Crabtree, Judy S.; Weitzman, Jonathan B.; Yaniv, Moshe; Burns, A. Lee; Chandrasekharappa, Settara C.; Collins, Francis S.; Spiegel, Allen M.; Marx, Stephen J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 19, 16.09.2003, p. 10770-10775.

Research output: Contribution to journalArticle

Agarwal, SK, Novotny, EA, Crabtree, JS, Weitzman, JB, Yaniv, M, Burns, AL, Chandrasekharappa, SC, Collins, FS, Spiegel, AM & Marx, SJ 2003, 'Transcription factor JunD, deprived of menin, switches from growth suppressor to growth promoter', Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 19, pp. 10770-10775. https://doi.org/10.1073/pnas.1834524100
Agarwal, Sunita K. ; Novotny, Elizabeth A. ; Crabtree, Judy S. ; Weitzman, Jonathan B. ; Yaniv, Moshe ; Burns, A. Lee ; Chandrasekharappa, Settara C. ; Collins, Francis S. ; Spiegel, Allen M. ; Marx, Stephen J. / Transcription factor JunD, deprived of menin, switches from growth suppressor to growth promoter. In: Proceedings of the National Academy of Sciences of the United States of America. 2003 ; Vol. 100, No. 19. pp. 10770-10775.
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