Extracellular signal-regulated kinase signaling regulates the opposing roles of JUN family transcription factors at ETS/AP-1 sites and in cell migration

Nagarathinam Selvaraj, Justin A. Budka, Mary W. Ferris, Joshua P. Plotnik, Peter Hollenhorst

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

JUN transcription factors bind DNA as part of the AP-1 complex, regulate many cellular processes, and play a key role in oncogenesis. The three JUN proteins (c-JUN, JUNB, and JUND) can have both redundant and unique functions depending on the biological phenotype and cell type assayed. Mechanisms that allow this dynamic switching between overlapping and distinct functions are unclear. Here we demonstrate that JUND has a role in prostate cell migration that is the opposite of c-JUN's and JUNB's. RNA sequencing reveals that opposing regulation by c-JUN and JUND defines a subset of AP-1 target genes with cell migration roles. cis-regulatory elements for only this subset of targets were enriched for ETS factor binding, indicating a specificity mechanism. Interestingly, the function of c-JUN and JUND in prostate cell migration switched when we compared cells with an inactive versus an active RAS/extracellular signal-regulated kinase (ERK) signaling pathway. We show that this switch is due to phosphorylation and activation of JUND by ERK. Thus, the ETS/AP-1 sequence defines a unique gene expression program regulated by the relative levels of JUN proteins and RAS/ERK signaling. This work provides a rationale for how transcription factors can have distinct roles depending on the signaling status and the biological function in question.

Original languageEnglish
Pages (from-to)88-100
Number of pages13
JournalMolecular and Cellular Biology
Volume35
Issue number1
DOIs
StatePublished - 2015

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Extracellular Signal-Regulated MAP Kinases
Transcription Factor AP-1
Cell Movement
Transcription Factors
Prostate
RNA Sequence Analysis
Carcinogenesis
Proteins
Phosphorylation
Phenotype
Gene Expression
DNA
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Extracellular signal-regulated kinase signaling regulates the opposing roles of JUN family transcription factors at ETS/AP-1 sites and in cell migration. / Selvaraj, Nagarathinam; Budka, Justin A.; Ferris, Mary W.; Plotnik, Joshua P.; Hollenhorst, Peter.

In: Molecular and Cellular Biology, Vol. 35, No. 1, 2015, p. 88-100.

Research output: Contribution to journalArticle

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